Journal of Cancer Biology

Short Communication Open Access

Machine learning methods for prostate cancer diagnosis

Abedalrhman Alkhateeb, Govindaraja Atikukke, Luis Rueda

Prostate cancer (Pca) is one of the most common cancers among men worldwide. The current screening methods lack effectiveness such as prostate-specific antigen (PSA) and Magnetic resonance imaging (MRI), and some others come with pain such as biopsy. Understanding the genomic behavior of the disease may play a key part in designing more effective, accurate, and less invasive diagnosis measures. Pca has many clinical features to describe the spread and the aggressiveness of the tumor including Gleason score, TNM staging system, and the location of the tumor in the prostate gland which is known as laterality.

Commentary Open Access

Network-based poly-pharmacological study sheds light on effective active constituents in Compound Kushen Injection preparations against lung cancer

Qian Cai, Hui-Heng Lin

Traditional Chinese Medicine (TCM), the world’s oldest known herbal medicine, has long been used in several Asian countries. Emerging evidence has demonstrated their effectiveness and safety in the treatment of various diseases, ranging from mild flu to severe cancers. A great number of patients have benefited by receiving TCM therapies. However, due to the complex chemical compositions of TCM, which could produce highly complex compound-protein binding interactions, the molecular mechanisms underlying the pharmacological actions of TCM still remain poorly understood. Specifically, it is difficult to identify and isolate the effective constituents from the mixture of many compounds, even the therapeutic targets are known.

Mini Review Open Access

Safety and efficacy of immune checkpoint inhibitors in cancer patients with pre-existing autoimmune disease 

Wint Yan Aung, MD, Margaret Locke, Adit Singhal, MD, Nagashree Seetharamu, MD

The advent of immune checkpoint inhibitors (ICI) targeting CTLA-4 and PD-1/PD-L1 pathways has revolutionized cancer treatment with significantly improved outcomes across a spectrum of cancers [1,2]. Although ICI therapy offers significant clinical benefits, these treatments can also lead to various immune-related adverse events (irAEs) that may negatively impact patient outcomes. Although the precise mechanism of irAE is not fully understood, they demonstrate many clinical features similar to autoimmune diseases. IRAEs are thought to result from bystander effects of activated T-cells, cross-reactivity between tumor and host tissues, and the role of the gut microbiome in immune activation [3].

Short Communication Open Access

Implications of the USP10-HDAC6 axis in lung cancer - A path to precision medicine

Xiaohong Mary Zhang, Navnath Gavande, Prahlad Parajuli, Gerold Bepler

Lung cancer is the leading cause of cancer death among both men and women in the United States. Because lung cancer is genetically heterogeneous, tailored therapy alone or in combination with chemotherapy would increase patient overall survival as compared with the one-size-fits-all chemotherapy. TP53-mutant lung cancer accounts for more than half of all lung cancer cases and is oftentimes more aggressive and resistant to chemotherapy. Directly targeting mutant p53 has not yet been successful, so identification of novel therapy targets and biomarkers in the TP53-mutant lung cancer is urgently needed to increase the overall survival in this subgroup.

Short Communication Open Access

Correlation of bone marrow morphologic assessment and genetic aberrations in plasma cell myeloma with clinical outcomes

Tayler van den Akker, Yansheng Hao, Julie Teruya-Feldstein

Plasma cell myeloma is a hematopoietic neoplasm with morphologic and genetic heterogeneity. Genetics have been shown to play an important role in risk stratification of plasma cell myeloma however the correlation between genetic aberrations and morphologic features is not well studied. In performing a systematic study of 266 multiple myeloma bone marrow biopsies from 329 patients, we initially investigated the association between bone marrow morphology, conventional cytogenetics, gene expression profiling and gene mutations

Review Article Open Access

Selectively depleting the energy of cancer cells: A new therapeutic paradigm

Hilmar M Warenius MA, MB, Bchir, PhD, FRCP, FRCR1

Over the past fifty years the somatic mutation theory of cancer has emerged as the most successful explanation of the molecular phenotype of human cancer cells. Normal non-mutated genes may, however, also play a role in carcinogenesis. In particular these may contribute to aerobic glycolysis and the potential interaction of PKM2 and Cdk4 in helping the nascent cancer cell avoid apoptosis by the interaction of their respective amino acid sequences: anionic SDPTEA and cationic PRGPRP. It is proposed that cancer first occurs in normal

Research Article Open Access

Evaluation of clinical outcomes in muscle-invasive bladder cancer patients based on molecular subtypes

Dina Moustafa Mouhamed Darwish, Asmaa Mohamed El-Kady, Darin Abd El-Aziz Mohamed Ali, Fatma Zakaria Hussein

Bladder cancer is the most common malignancy involving the urinary system and the tenth most common malignancy worldwide. Bladder cancer is the fourth most common cancer and the fifth most leading cause of cancer death in Egypt. This study aimed to assess all patients’ molecular subtypes (basal & luminal) of muscle-invasive bladder cancer and its impact on response to neoadjuvant chemotherapy and survival.

Research Article Open Access

Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer

Desta Beyene, Tammey Naab, Victor Apprey, Luisel Ricks-Santi, Ashwini Esnakula, Mustafa Qasim, Matthew George, Karen G Minoza, Robert L Copeland Jr, Carolyn Broome, Yasmine Kanaan

Eight protein biomarkers (ER, PR, HER2, Cyclin A2, Cytokeratin 5, Vimentin, Bcl2, and Ki-67) were evaluated using tissue microarrays (TMAs) and immunohistochemistry (IHC). The IHC results from TMAs were analyzed by both supervised and unsupervised clustering methods. The predictive clusters for the supervised and unsupervised methods were compared for agreement with the empirical classification. Kappa values were used to determine the overall percent correct clusters and agreement between specific clusters.

Commentary Open Access

Advances in glyconanotechnology based biomedical applications

Divya Kamath, Stefan H. Bossmann

There is an emerging awareness in cancer biology that glycobiology plays a significant, if not decisive role in oncogenesis, tumor survival, and proliferation. The human glycome is even more complex than the human genome, because glycans are synthesized as secondary gene products by sequentially acting glycosidases and glycosyltransferases. Glycans act as a communication system within the organism and between different organisms.

Case Report Open Access

Granular cell tumor (Abrikossoff's tumor) of the tongue: A case report

Pedro Dias Ferraz

Granular cell tumor, also known as Abrikossoff’s tumor, is a benign tumor that is relatively rare and is slightly more common in female patients, with a higher prevalence between the fourth and sixth decades of life although it is possible to appear at any age. It can appear in any part of the body but about 45-65% of all the lesions appear in the head or neck areas. Intraoral lesions represent about 70% of these cases.

Commentary Open Access

CD133 and centrosomes: How CD133 inhibits autophagy and induces the undifferentiated state of cancer cells at centrosomes

Hideki Izumi

CD133 is a transmembrane protein that mainly localizes to the plasma membrane of normal stem cells as well as cancer stem cells, and is widely known as a cancer stem cell marker. CD133 was recently shown to localize in the cytoplasm; however, its transport pathway and functions currently remain unknown.

Short Communication Open Access

Perturbation of cellular integrity by nicotine: A major component of e-cigarette smoke

Suthakar Ganapathy, Qiang Zhang, Takashi Nishioka, Alexandros Makriyannis, Changyan Chen

In recent years, the use of electronic cigarettes (e-cigarettes) or “vape” in which nicotine is the major component has been dramatically increasing, particularly among teenagers and young adults. This is due to a general perception that e-cigarettes are harmless to use, in particular for the cessation of tobacco smoking. Thus, a better understanding of whether e-cigarettes pose a risk to human health is urgently needed. Nicotine exposure can accelerate malignant growth of cancer cells.

Review Article Open Access

Role of H3K9 demethylases in DNA doublestrand break repair

Hee-Young Jeon, Arif Hussain, Jianfei Qi

H3K9 demethylases can remove the repressive H3K9 methylation marks on histones to alter chromatin structure, gene transcription and epigenetic state of cells. By counteracting the function of H3K9 methyltransferases, H3K9 demethylases have been shown to play an important role in numerous biological processes, including diseases such as cancer. 

Review Article Open Access

Mechanisms of cancer cell rescue against pancreatic cancer therapeutics: Intrinsic and acquired resistance

Jeevan Ghosalkar, Vinay Sonawane, Kalpana Joshi

Pancreatic Cancer (PC) with dismal prognosis poses a significant challenge to healthcare systems worldwide. PC is the fourth leading cause of cancer-related mortality globally and is projected to surpass lung cancer as the second foremost cause by 2030. The poor prognosis associated with PC is primarily due to the low rate of early detection, rapid progression, and limited treatment options. Chemotherapy remains a cornerstone of treatment for PC in all stages of disease.

Mini Review Open Access

The many faceted role of glycogen synthase kinase-3 (GSK-3) in T cells and cancer immunotherapy

Aurora Rivas Crespo, Silvia Guil Luna, Bastien Moës, Antonio Rodriguez, Christopher E Rudd

Originally identified for its involvement in phosphorylating glycogen synthase and regulating glucose metabolism in response to insulin, glycogen synthase kinase-3 (GSK-3) has since been recognized as a versatile serine/threonine kinase with diverse functions [1,2]. Extensive research has demonstrated that GSK-3 phosphorylates over 100 protein substrates where it intersects numerous signaling pathways. While it was initially implicated in the regulation of glucose metabolism, subsequent investigations revealed an impact of GSK-3 in cellular processes beyond glycogen synthase phosphorylation and glycogen metabolism [3].

Review Article Open Access

Cancer and microenvironment: who and where is the enemy? old problem, new regards

Kambiz Afrasiabi

Living cell could be considered the most sophisticated anti-entropy machinery born in the heart of the strong and ferocious pro-entropy environment of the primordial ocean full of boiling and salty water, some thirty-eight hundred million years ago on this planet. Evolution of prokaryotes with a simple cell membrane to eukaryotes and later on multi-cellular organisms, has necessitated the birth and evolution of a protective microenvironment, which could shield and secure evolution of living organisms by its sophisticated anti-entropy components

Commentary Open Access

Efficiency metrics in cancer care

Matt Hickey, Adele Youngs, Eduardo Pisani

Inefficient care is a leading factor in poorer outcomes for patients. According to the OECD, one-fifth (20%) of healthcare expenditure either does not improve people’s health or could worsen their outcomes [1]. In addition, the World Health Organisation estimates that 40% of health spending is wasted through inefficiency.

Commentary Open Access

The Oncogenic Role of ADAR1-Mediated RNA Editing in Thyroid Cancer

Julia Ramírez-Moya, Pilar Santisteban

A-to-I RNA modifications performed by the adenosine deaminase acting on RNA (ADAR) protein family are gaining traction as important mechanisms in cancer biology. A-to-I RNA editing changes adenosine to inosine on double stranded RNA, which co-transcriptionally alters transcript sequence and structure. A number of microRNA (miRNA) precursors are known to be edited by the ADARs, which alters the expression and/or function of the mature miRNA. 

Mini Review Open Access

Biological basis for concurrent chemoradiation in head and neck cancer: Timing matters

Allen M. Chen, M.D., M.B.A.

Given that the addition of cytotoxic chemotherapy to radiation has been shown to improve overall survival and local-regional control for select patients with head and neck cancer, concurrent chemoradiation constitutes a mainstay of treatment. In pre-clinical studies, platinum-based chemotherapy, when delivered concurrently with radiation, is intended to serve as a radio-sensitizer, potentiating the cytotoxic effects of radiation on proliferating squamous cell carcinoma cells. From a biological basis, it is thus advisable that patients begin chemotherapy

Review Article Open Access

PARP inhibitors in HRD BRCAness breast cancer patients

Inês Eiriz, Marta Vaz Batista, Ana Rita Freitas, Telma Martins, Catarina Machado, Sofia Braga, Catarina Santos

Breast Cancer patients with germline Breast Cancer Gene (BRCA) mutations have a greater advantage from targeted therapy with Poly (ADP-ribose) Polymerase (PARP) inhibitors (PARPi). The identification of patients with homologous recombination deficiency (HRD) tumors that may be sensitive to PARPi besides those with germline BRCA1/2 mutations remains an important point of research.

Review Article Open Access

Tumor biomarkers from discovery to clinical practice

Malik Suleman Naseem

A tumor marker is a chemical that acts as a tumor indication. Tumor biomarkers are undefined in origin, but they indicate the existence of a certain tumor. The detection of a specific tumor is aided by an increase or decrease in the concentration of marker concentrations. Gene expression arrays, proteomic technologies, and high-throughput sequencing are some of the current methods for detecting cancer.

Commentary Open Access

Machine learning for precision medicine in cancer: Transforming drug discovery and treatment

Sachin Kumar Deshmukh

Machine learning (ML) is a branch of artificial intelligence that uses an algorithm to process the data, retrieve valuable information, learn from it, find a pattern, and make predictions. Manual data analyses suffer from several disadvantages including it is time-consuming and subject to error.

Mini Review Open Access

Navigating alopecia: Practical guidelines for minimizing hair loss in CyberKnife stereotactic radiosurgery for calvarial or scalp tumors

David J. Park, MD, PhD, Steven D. Chang, MD, MBA

Hair loss, or alopecia, is a common yet underdiscussed side effect of stereotactic radiosurgery (SRS), particularly affecting patients undergoing treatment for calvarial or scalp tumors [1]. The psychological and emotional impacts of alopecia are profound, affecting patients' quality of life and, in some cases, influencing treatment decisions [2-4]. Despite its significance, there has been a lack of specific guidelines aimed at preventing this adverse effect. The study led by the team from Stanford University's Department of Neurosurgery

Commentary Open Access

Cryoablation is a safe alternative to surgery for low-risk breast cancer

Khan SY, Chu V, Melkus MW, Layeequr Rahman R

Cryoablation of breast cancer offers an alternative to surgery for women who are not ideal surgical candidates. It is a minimally invasive procedure that has already had success in fibroadenoma treatment with good tumor reduction and cosmesis. The findings of cryoablation as treatment for early-stage, low-risk breast cancer has been previously discussed in the recently published article ‘Cryoablation: A promising non-operative therapy for low-risk breast cancer’.

Review Article Open Access

C/EBPα-mediated epigenetic control of liver disorders in young children

Ruhi Gulati, Nikolai Timchenko

Despite a young age and limited exposure to nutritional challenges and other diseases, young children can develop liver disorders such as fatty liver, fibrosis, and liver cancer. The preliminary stages of these disorders are silent, and the patients come to the clinic at a late stage. During studies of pediatric liver cancer hepatoblastoma (HBL), our group found that a portion of our fresh HBL biobank is characterized by the development of Non-Alcoholic Fatty Liver Disease (NAFLD) including fatty liver, fibrosis, and increased proliferation. Our studies and other 

Mini Review Open Access

Cancer stem cells as a biomarker – A mini review

Urja Joshi, Dhara Jani, Linz-Buoy George, Hyacinth Highland

Cancer stem cells (CSCs) also known as tumor stem cells (TSCs), are pivotal in cancer development and progression. They can be identified through specific markers and surface proteins (e.g., CD44, CD133) that differ from those on non-CSC tumor cells. As well high CSC levels often correlate with poor prognosis, aggressive disease, and resistance to conventional therapies. CSCs are more resistant to standard treatments like chemotherapy and radiation, leading to relapse and metastasis. 

Review Article Open Access

The rising tide of pancreatic adenocarcinoma: A review of risk factors, diagnostic challenges, and treatment updates

Ethan A. Burns, Maen Abdelrahim

Pancreatic ductal adenocarcinoma (PAC) is an aggressive malignancy that is frequently locally invasive or widely metastatic at the time of diagnosis. As such, morbidity and mortality remain extremely high. Despite growing advances in surgical technique and medical management, the incidence and mortality rate are expected to increase over the next two decades. 

Research Article Open Access

COVID-19 in patients with and without cancer: Examining differences in patient characteristics and outcomes

Nihal E. Mohamed, Emma KT. Benn, Varuna Astha, Qainat N. Shah, Yasmine Gharib, Holden E. Kata, Heather Honore-Goltz, Zachary Dovey, Natasha Kyprianou, Ashutosh K. Tewari

This study examines differences between patients with and without cancer in patient demographic and clinical characteristics and COVID-19 mortality and discusses the implications of these differences in relation to existing cancer disparities and COVID-19 vulnerabilities. Data was collected as a part of a retrospective study on a cohort of COVID-19 positive patients across Mount Sinai Health System from March 28, 2020 to April 26, 2020. Descriptive, comparative, and regression analyses were applied to examine differences between patients with and without cancer in demographic and clinical characteristics and COVID-19 mortality and whether cancer status predicts COVID-19 mortality controlling for these covariates using SAS 9.4. Results showed that, of 4641 patients who tested positive for COVID-19, 5.1% (N=236) had cancer.

Review Article Open Access

Toward a new approach to treating tumors: Inducing apoptosis by combining chemotherapy and mild hyperthermia

James R. Paulson

Our studies on the effects of mild hyperthermia (≤ 42°C) on prometaphase-arrested and interphase HeLa cells are reviewed. Mild heat treatment rapidly induces apoptosis in H-HeLa cells that have been arrested in prometaphase with spindle poisons. This is shown by the appearance of morphological changes characteristic of apoptosis, the activation of Caspase 3, and the fact that the changes are blocked by caspase inhibitors such as zVAD-fmk. The same treatment does not cause apoptosis in interphase cells, or in prometaphase-arrested cells of other HeLa strains such as HeLa S3, MKF, and WML. However, prometaphase-arrested cultures of those other HeLa strains can be made sensitive to mild heat treatment by simultaneous exposure to compounds such as navitoclax (ABT-263) which inhibit Bcl-2 family anti-apoptotic proteins. Interphase cells can be made sensitive to 42°C treatment by combining ABT-263 or ABT-199 with S63845, a potent and selective inhibitor of MCL-1.

Review Article Open Access

From nitrogen mustard to nano-machines: A journey through cancer therapeutics evolution

Kambiz Afrasiabi, M.D.

The history of cancer therapeutics since its birth some eighty years ago has gone through a tortuous path guided by understanding of the mechanism of carcinogenesis and notorious for many excitements and frustrations. The birth of nitrogen mustard in 1940’s through a serendipitous observation during the Second World War, was guided by the perception that a poison that kills normal cells, could also kill cancer cells. The excitement generated by shrinkage of tumor mass was soon followed by disappointment and frustration caused by tumor regrowth. 

Commentary Open Access

Changing the landscape of non-small cell lung cancer disparities

Joab O. Odera, Muthana Al Abo, Steven R. Patierno, Jeffrey M. Clarke, Jennifer A. Freedman

In the United States, lung and bronchus cancers are the second most common types of cancer and are responsible for the largest number of deaths from cancer, with African Americans suffering disproportionately from lung and bronchus cancers. This disparity likely results from a complex interplay among social, psycho-social, lifestyle, environmental, health system, and biological determinants of health.

Review Article Open Access

Regulation of ETS family of transcription factors in cancer

Aiindrila Dhara, Sourav Ghosh, Nirmalya Sen

E-26 Transformation Specific (ETS) transcription factors are known to cause various cancers and their aberrant expression has been related to various oncogenic processes like metastasis and angiogenesis. Currently very few drugs exist which can directly target oncogenic transcription factor and none of them are approved for human use. To design ETS transcription factor targeting small molecules, an understanding of their regulation in cancers is essential. In this review, we have discussed upstream transcriptional regulations of ETS factors that includes epigenetic

Review Article Open Access

Nuclear mTORC2 and its emerging role in gene regulation

Moinuddin, Narayan Kumar, Smrati Bhadauria

The mechanistic target of rapamycin (mTOR), a critical regulator of cell growth, metabolism, survival, and actin-cytoskeletal organization, is primarily recognized for its cytoplasmic functions. However, emerging evidence suggests that the mTOR and its constituent partners also localize to the nucleus, where it may play distinct roles in gene expression regulation, chromatin remodeling, and transcriptional control. This review highlights the evolving understanding of nmTORC2 (nuclear mTORC2), with a particular focus on its composition, functional implications, and relevance in cancer biology.

Commentary Open Access

Proteomic research and protein biochemistry for targeted therapy of anti-cancer drugs

Hui-Heng Lin

Despite the advancements of medical care and pharmaceutical technologies, unfortunately in recent decades, epidemiological surveys have identified that the population of cancer patients are indeed increasing in multiple regions. So, cancers go on threatening human health and life to a larger and larger extent. A series of special anti-cancer drugs are known as “targeted therapies”.  Those anti-cancer drugs work through blocking bioactivities of specific onco-gene or onco-protein so as to prevent the progressions of cancers.

Editorial Open Access

Tumor evolution: The road map to future cancer therapeutics

Kambiz Afrasiabi, M.D.

The common denominator among all is ignoring the most fundamental pillar on which the forward move of tumor mass is based, namely tumor evolution along the thermodynamics arrow of time. Tumor evolution in certain ways is akin to evolution of life on this planet, which has acquired higher levels of sophistication and diversity. Neoplastic transformation and its evolutionary path could be divided into three main phases: initiation, promotion, and progression. Our future cancer therapeutics is expected to intercept with this evolutionary path. This necessitates a deep understanding of the dynamics of this path, and the necessary means including AI, and Nano–delivery to execute this task.

Review Article Open Access

Sézary's syndrome: Review of the clinical, histomorphological and diagnostic aspects of a rare cutaneous lymphoma

Miguel Augusto Martins Pereira, Lucas Natã L. Silva

Sézary's Syndrome consists of a rare type of non-Hodgkin cutaneous T-cell lymphoma (CTCL), being a very aggressive leukemic variant of CTCL. Given its rarity and its ability to mimic other more common diseases, this neoplasm represents a major diagnostic challenge for both clinicians and pathologists.

Review Article Open Access

Precision medicine and immunotherapy advances transforming colorectal cancer treatment

Tamer A. Addissouky, Ibrahim El Tantawy El Sayed, Majeed M. A. Ali, Mahmood Hasen Shuhata Alubiady, Yuliang Wang

New stool DNA panels and blood-based assays offer non-invasive options for early CRC detection, though require further validation. Immuno- and targeted therapies matched to tumor molecular profiles have transformed metastatic CRC treatment. Pembrolizumab elicits durable responses in mismatch repair-deficient tumors, and anti-EGFR antibodies cetuximab/panitumumab improve outcomes for left-sided RAS/RAF wild-type CRC. Larotrectinib and entrectinib are highly active in NTRK fusion-positive CRC. Research focusing on new immunotherapies, leveraging the microbiome, and combining multi-omics data to enable precision medicine holds promise. Disparities across groups remain a challenge.

Commentary Open Access

Renoprotective effect of direct renin inhibitor (aliskiren) during partial ureteral obstruction

Ahmed Elkashef

Partial ureteral obstruction (PUO) is a major clinical problem in the daily urologic practice that is treatable and often reversible. Renin-angiotensin system (RAS) is implicated in the pathophysiology of PUO as angiotensin II induces alterations in renal hemodynamics, apoptosis, inflammation and fibrosis. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have been clinically used to recover the unfavorable functional and histological changes after relief of PUO.

Editorial Open Access

Tumor microenvironment: The crossroad of normal state and cancer

Kambiz Afrasiabi, M.D.

The identification of comprising cells and composition of microenvironment, which is the result of many years of work in many research labs across the globe, has made it possible to see just the tip of iceberg. The dynamic and fluid nature of microenvironment, with its tumor agonistic and antagonistic cells at one end, and its intricate communication with tumor mass, is leaving us with many unanswered questions, both conceptually and functionally. Tumor associated macrophages, tumor associated fibroblasts, B and T regulatory cells, angiogenesis factors and many other cellular, and humeral factors, comprise elements of tumor microenvironment eco-system. Tissue resident macrophages, originating from bone marrow are among the tumor antagonists. However, the most puzzling of all are tissue resident macrophages that originate from the yolk sac of embryo and dispersed in all organs.

Commentary Open Access

Challenges in the humanized mouse model for cancer: A commentary 

Eric Ramirez-Salazar, Meenhard Herlyn, Rajasekharan Somasundaram

The complexity of the tumor microenvironment has been a challenge for understanding the mechanisms of therapy resistance. The development of improved animal models that closely mimic human disease is key for understanding and treating diseases. Recently, a new humanized mouse model has been developed that enables the study of human immune cells in tumor host-cell interactions

Research Article Open Access

Investigation of CBL-b, c-CBL expressions in colorectal cancer patients and their relationship with clinicopathological characteristics

Reyhaneh Yarmohammadi, Minoo Pargol, Zahra Mozooni, Leyla Bahadorizadeh, Sara Minaeian, Shadi Tajvidi

Colorectal cancer (CRC) is the most common gastrointestinal cancer and a major cause of cancer-related mortality worldwide. Molecular indicators of pathogenic factors that regulate CRC, which are known as oncogenes, are desirable for response to treatment and improvement of CRC patient management. Several risk factors play a role in the development of this disease, which can occur genetically, familial, or sporadically. CRC tumorigenesis is stimulated by the proto-oncogene β-catenin (wnt/β-catenin). Casitas B-lineage lymphoma (c-Cbl) inhibits CRC tumor growth through an unknown mechanism that affects nuclear β-catenin. The current objective of this study is to evaluate the expression levels of Cbl-b and c-Cbl genes to determine if their transcripts can be used as suitable diagnostic indicators. Additionally, we aim to investigate the correlation between clinicopathological information of CRC patients and the levels of Cbl-b and c-Cbl.

Short Communication Open Access

Advances in the investigation of the Epstein Barr Virus (EBV) in Colombia during the last 20 years

Daniela Arturo-Terranova

Epstein Barr Virus (EBV) belongs to the family Herperviridae, subfamily Gammaherpesvirinae, genus Lymphocriptovirus [1]. It is one of the most common human viruses as most people get infected with EBV at some point in their lives. EBV spreads most commonly through bodily fluids, primarily saliva. Although viral DNA has been detected in breast milk and genital secretions [2], the evidence for sexual transmission is extremely limited [3]. 

Short Communication Open Access

Fertility treatments for men with hypogonadotropic hypogonadism

Guy Morris, David J. Cahill

The diagnosis of azoospermia is a devasting one for men – and it represents the obliteration of so many unspoken hopes and expectations. Most causes of azoospermia are not amenable to treatment but those due to hypogonadotropic hypogonadism can respond to gonadotropin therapy. This can be a lengthy and expensive treatment, but it delivers an opportunity to men to restore, albeit temporarily, their production of sperm. Encouragingly, treatment is associated with good success rates, even outside of specialist clinics. 

Review Article Open Access

Targeting the PRMT1-cGAS-STING signaling pathway to enhance the anti-tumor therapeutic efficacy

Daoyuan Huang, Abdol-Hossein Rezaeian, Jingchao Wang, Yihang Qi, Hong Chen, Hiroyuki Inuzuka, Wenyi Wei

Activating innate immune signaling in tumor cells to enhance anti-tumor immunity and increase T cell-mediated killing is the core objective of tumor immunotherapy. PRMT1, one of the most crucial PRMTs, plays a critical role in tumor progression and innate immunity. Recent research revealed that PRMT1 can inhibit the enzymatic activity of cGAS in part through PRMT1-mediated Arg methylation, thereby suppressing the anti-tumor immune response of cells. As such, inhibiting or knocking down PRMT1 can synergistically enhance the efficacy of anti-PD-1 immunotherapy by activating the cGAS-STING signaling pathway. Here, we provide a comprehensive description of the two key signaling components, PRMT1 and cGAS, in the PRMT1-cGAS-STING signaling pathway for therapeutic intervention to augment anti-tumor immunity. By understanding the specific physiological functions and regulatory mechanisms of PRMT1.

Original Research Open Access

Effectiveness of comprehensive nursing intervention on alleviating postoperative fatigue and anxiety in patients with oral cancer

Sukanta Nath, Khemchand Falwaria, Shiromani Debbarma, Matrujyoti Pattnaik, Ankita Debnath

Postoperative functional impairments are common in patients with oral cancer following surgery. Furthermore, these patients frequently experience fatigue and anxiety, which are strongly linked to a lower quality of life (QOL). The goal of our study was to investigate the effectiveness of comprehensive nursing intervention on alleviating postoperative fatigue and anxiety in patients with oral cancer.

Commentary Open Access

The role of exercise and physical activity in osteosarcoma for patients and survivors

Miriam B. Garcia, Keri Schadler

Exercise has been found to improve function, mitigate disability, enhance the anticancer immune system response, and improve quality of life for patients with osteosarcoma and its survivors. Of late, exercise has additionally been implemented as an adjuvant to standard therapies. These products of exercise, along with the benefits of physical activity in pre- and postoperative rehabilitation, were summarized in the recently published book chapter Exercise and Physical Activity in Patients with Osteosarcoma and Survivors.

Commentary Open Access

Turn up the MIC(A/B): Amplifying stress-ligand recognition to target iPSC derived immune cell therapies against tumors and diseased cell states

John Goulding, Alejandro J. Garcia, Martin P. Hosking, Peter Szabo, Bahram Valamehr

Cancer is a multifaceted disease that is overwhelming in the breadth and scope of its genetic diversity, tissue pathology, and response to therapy. In recent years, the development of novel chimeric antigen receptor (CAR) containing cell-based therapies has provided significant clinical benefit to patients with certain hematological malignancies. The overall response rates (ORR) of Food and Drug Administration (FDA) approved autologous CD19 CAR T cell products for the treatment of refractory and relapsed B cell lymphomas have reached approximately 80% in defined patient populations, with durable remissions of greater than several years. Regrettably, the deployment of these novel cell-based therapies against solid tumor indications has garnered much less enthusiasm due to disappointing clinical success. The intrinsic adaptability of solid tumors makes them particularly elusive for effective targeted treatment, in part due to their extensive cellular heterogeneity and antigen diversity, their capacity to evade immune responses through antigen escape, and their ability to establish immune suppressive microenvironments. Identifying and selecting appropriate tumor specific antigens that distinguish tumor cells from healthy tissue remains arguably one of the most essential requirements to develop efficacious solid tumor targeting cell-based therapies.

Review Article Open Access

Spatial entropyomics: The path to future cancer therapeutics

Kambiz Afrasiabi, M.D.

The hallmark of neoplastic transformation is a significant increase in master regulator complex network entropy of cancer cell. This happens as a result of breakdown of the fine interplay of the second law of thermodynamics with the living cell. The methodologies that have been employed towards elucidation of spatial genomics and polyomics of tumor mass, could be applied towards the generation of spatial master

Commentary Open Access

Chromatin dynamics: Nucleosome occupancy and sensitivity as determinants of gene expression and cell fate

Jane Benoit, Mahdi Khadem Sheikhbahaei, Jonathan Dennis

The nucleosome, consisting of ~150bp of DNA wrapped around a core histone octamer, is a regulator of nuclear events that contributes to gene expression and cell fate. Nucleosome organization at promoters and their associated remodeling events are important regulators of access to the genome. Occupancy alone, however, is not the only nucleosomal characteristic that plays a role in genome regulation. Nucleosomes at the transcription start sites (TSSs) of genes show differential sensitivity to micrococcal nuclease (MNase) and this differential sensitivity is linked to transcription and regulatory factor binding events. 

Short Communication Open Access

Plasma oncology - Physical plasma as innovative tumor therapy

Matthias B. Stope

In medical diagnostics, complex physical techniques are state of the art and everyday clinical practice would be unthinkable without them. But also, in the field of therapeutic interventions there are several physical procedures. For example, ionizing radiation is used in oncology and non-ionizing radiation in dermatological (UV light) and photodynamic therapies (laser). Similarly, electrosurgical and laser procedures are well established in surgery.

Mini Review Open Access

Targeting m6A in cancer – new prospective

Grossmann L.D, Moshitch-Moshkovitz S

The field of mRNA modifications has rapidly developed over the last years, outlining a new realm of gene expression regulation that appears to play a major role in health and disease states including cancer. Considering the information regarding chemical modifications of DNA and proteins, decades of research proved beyond any doubt that chemical modifications affect chromatin structure as well as enzymatic activity.

Review Article Open Access

The role of certain neurotransmitters in the emergence and progression of malignant tumors, and the potential of using neurotransmitter antagonists to block the carcinogenic effect of the tumor stroma

Viktor Shtilbans

Within the last ten years, there has been a growing body of data on the potential of neurotransmitter blockers as promising components of comprehensive cancer treatment. Neurotransmitters play an important role in the intercellular communication of the various tumor cells: malignant epithelial cells, myofibroblasts, tumor-associated macrophages, stromal cells, and endothelial cells of the tumor vasculature. In particular, they are responsible for the cells’ resistance to chemotherapy.

Commentary Open Access

Co-infection, re-infection and genetic evolution of SARS-CoV-2: Implications for the COVID-19 pandemic control

Wagner Gouvêa dos Santos

The identification of new mutations in SARS-CoV-2 and their roles in the viral fitness towards evolution and survival to face the selective pressure imposed by the human host immune response have become the target of great attention recently. As result, concerns related to the emergence of novel variants with more transmissibility and pathogenic potential have led many countries to apply more restrictive measures to avoid increase in the number of infections and collapse of healthcare systems.

Commentary Open Access

DKK2 mediated immunosuppressive pathway and angiogenesis for colon cancer progression

Zhengxi Chen, Qian Xiao

Available targeted therapies for colorectal cancer (CRC) are limited. Immunotherapy offers new options for cancer treatment, but most of CRC are refractory to current immune checkpoint blockade, which indicates the possible presence of yet uncharacterized immune-suppressive mechanisms. Herein we report that high levels of Dickkopf-related protein 2 (DKK2) are expressed in human CRC tumors, and the DKK2 blockade caused stronger activation of tumor-infiltrating CD8+ T cells in ex vivo culture. A correlation of high DKK2 expression 

Editorial Open Access

Digital oncology, the dawn of a new era turning the clock back on tumor mass

Kambiz Afrasiabi, M.D.

Success in any field, especially in cancer medicine, is based on embracing evolution in understanding other scientific fields [4] and its application to the forward move in cancer therapeutics. As such, we have gone through discovery of a diverse group of therapeutics, targeting different sub compartments of growth and proliferation pathways [5] and taking advantage of their synergistic efficacy, in different combinations [6]. Dissection of immune regulatory pathways [7] and their interaction with cancer cell has led to the generation of modern immune therapeutic agents. Single-cell sequencing technology [8] has paved the way for the development of spatial omics [9], which has opened the way on deeper understanding of tumor evolutionary path [10]. This would give us the opportunity to design a new generation of cancer therapeutics [11] intercepting with the forward evolutionary path of tumor mass.

Short Communication Open Access

Reflex ordered testing for molecular biomarkers in lung adenocarcinoma: An update

Debbie R. Walley, Jessica S. Thomas

Molecular biomarker testing is essential to the work up of metastatic and advanced non-small cell lung carcinoma. Despite molecular testing guidelines proposed by the National Comprehensive Cancer Network, Association for Molecular Pathology, and many others, multiple reports continue to indicate that lung cancer patients are inadequately tested for key molecular biomarkers. Within our hospital system, reflex ordered testing of a panel of molecular biomarkers in all newly diagnosed lung adenocarcinomas was approved and implemented in 2017.

Review Article Open Access

Entropy and cancer: The Future of cancer therapeutics

Kambiz Afrasiabi

Evolution of our thinking and design of cancer therapeutics has gone through a tortuous path in the last eighty or so years, since the first patient was treated with a chemical agent. Introduction of nitrogen mustard in the treatment of cancer in 1940’s was based on a serendipitous finding and observation during the second world war.

Commentary Open Access

Oncogenic specificity in nevus and melanoma formation

Konrad Kaminiow, Stephen M Ostrowski, David E Fisher

There is striking clinical, histological, and molecular diversity observed across melanocytic tumors. Activating mutations in BRAF and NRAS are well-established initiators of benign melanocytic nevi and melanoma. However, accumulating evidence reveals that the biological outcome after oncogene activation is dependent on cellular state differences that vary by anatomic site, developmental timing, and cell of origin.

Review Article Open Access

Proton sensing GPCR’s: The missing link to Warburg’s oncogenic legacy?

Jessica Cornell, Samantha Rea, Leif R Neitzel, Charles H. Williams, Charles C. Hong

A century after Otto Warburg's seminal discovery of aerobic glycolysis in cancer cells, a phenomenon dubbed the "Warburg effect", the mechanistic links between this metabolic rewiring and tumorigenesis remain elusive. Warburg postulated that this enhanced glucose fermentation to lactate, even in the presence of oxygen, stemmed from an "irreversible respiratory injury" intrinsic to cancer cells. While oxidative phosphorylation yields higher ATP, the Warburg effect paradoxically persists, suggesting that the excess lactate and acid production are worth the deficit. Since Warburg's discovery, it has been demonstrated that the acidic tumor microenvironment activates a myriad of pro-oncogenic phenotypes ranging from therapeutic resistance to immune escape. Here we propose that proton-sensing G-protein-coupled receptors (GPCRs) act as crucial heirs to Warburg's findings by transducing the acid signal from elevated glycolytic lactate into pro-oncogenic signals.

Short Communication Open Access

Telangiectatic osteosarcoma: A bare bones account

Bruce Rothschild, Jeno Sebes

Examination of the surface of bones (from which soft tissues have been removed) provides a window complementary to that provided by clinical, standard anatomic, laboratory and radiologic studies. That approach, utilized successfully for analysis of other forms of osteosarcoma is applied to the high grade telangiectatic version of medullary osteosarcoma.

Commentary Open Access

Can electronic-cigarette vaping cause cancer?

Moon-shong Tang, PhD, Yen-Len Tang, MD

The relative safety of E-cigarette (E-cig) has been an emerging topic in the public domain as well as the medical and scientific communities as vaping associated health problems arose. While there were  significant amounts of intelligent discussions and opinions on the benefits and deleterious effects of E-cig vaping, there is a lack of solid evidence of the fundamental biochemical and biological effects of E-cig aerosol and nicotine.

Commentary Open Access

FHIT as a biomarker for early screening of adult T-cell leukemia

Marcia Bellon, Christophe Nicot

Adult T-cell leukemia (ATL) is an incurable leukemia deriving from human T-cell leukemia virus (HTLV-I) infected cells. In our most recent study, we discovered that methylation of the tumor suppressor, fragile histidine triad gene (FHIT), exists in the majority of acute and chronic ATL patients. Methylation was seen in non-tumorigenic cells, in cells with low levels of HTLV-I integrated DNA, in longitudinal samples from HTLV

Commentary Open Access

Advances in the understanding of health disparities in the United States Hispanic population

Asma Pinkey, Masuma Anzuman, Mrudang Desai, Anna M. Eiring

Health disparities have become a major concern for global public health, disproportionately affecting minority and underserved populations throughout the United States (U.S.). Hispanics make up the fastest-growing minority group in the U.S., and they often experience significant health disparities when it comes to chronic diseases such as cancer, cardiovascular disease, and diabetes. These disparities are likely driven by a confluence of socioeconomic disadvantages, structural inequities, environmental exposures, and cultural barriers.

Commentary Open Access

Injectable hydrogel of biopolymers as controlled drug-delivery vehicle for melanoma treatment: A commentary

Swapan Maity, Pralay Maiti

Melanoma is a strongly incursive cancer situated in the skin with narrow consecutive therapies. The goal of this article is to reveal some of the latest advances in using hydrogel for cancer especially melanoma therapy. Biocompatible brush biopolymer (linear dextrin) graft with polyurethane is developed for monitoring the hydrophilic and hydrophobic equipoise for regulating the delivery of drug to the target region. Drug incorporated brush copolymers upon embedded in gelating agent (methyl cellulose) develop an injectable hydrogel with potential 

Review Article Open Access

Immuno-oncologic care during COVID-19: Challenges and opportunities for improving clinical care and investigation

Kristen Spencer, Eric A. Singer, Eugenia Girda

Cancer care has been greatly impacted during the COVID-19 pandemic. The number of cases and deaths caused by the COVID-19 pandemic continues to escalate throughout the United States and the world. Worldwide, over 150 million people have been diagnosed with the coronavirus and more than 3 million have died.

Commentary Open Access

Epigenetic alterations as diagnostic and therapeutic targets in breast cancer

Shahab Uddin

The incidence of breast cancer (BC) worldwide is on the rise due to reasons such as late detection, limited treatment choices for certain BC subtypes, and the development of drug resistance. These factors combined lead to unfavorable clinical results. Recent studies highlight the crucial significance of epigenetic changes in the development of BC, especially in relation to medication resistance and the preservation of stemness traits. Continuing research in the field of epigenetics and breast cancer carcinogenesis is crucial for overcoming present challenges and advancing our knowledge in this area, ultimately resulting in better outcomes for patients.

Mini Review Open Access

Thyroid cancer-tumor immune microenvironment (TIME) spatial transcriptomics reveals novel players

Shafiya Imtiaz Rafiqi, DVM, PhD, Juan Carlos Jaume, MD

Thyroid cancer (TC) encompasses several pathological types, notably papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), medullary thyroid cancer (MTC), and anaplastic thyroid carcinoma (ATC). While PTC accounts for the most common type, ATC, despite representing only 1–2% of all TC cases, is recognized as the most lethal and treatment-resistant endocrine malignancy. Despite sharing a common cellular origin, these two subtypes differ markedly in their clinical trajectories, response to therapy, and immune profiles. 

Short Communication Open Access

The intrinsically disordered DPF3 zinc finger protein: a promising new target in cancer therapy

Julien Mignon, Tanguy Leyder, Catherine Michaux

Cancer is a worldwide human disease of great concern, in which proteins are known to be highly involved, especially the group of intrinsically disordered proteins (IDPs). Due to their disorder-associated properties and floppy structure, IDPs remain difficult to target, requiring the design of new anticancer strategies. In that context, the zinc finger protein DPF3 has been identified as an amyloidogenic 

Commentary Open Access

BCG immunotherapy: Celebrating the past and looking to the future

Niyati Lobo, Ashish M. Kamat

2021 marks the centenary of the bacillus Calmette-Guérin (BCG) vaccine. In our review ‘100 Years of BCG Immunotherapy: From Cattle to COVID-19’, we highlight key milestones in the history of BCG, beginning from its discovery by Alfred Calmette and Camille Guérin to its present day use in tuberculosis (TB) prevention and as intravesical therapy for non-muscle-invasive bladder cancer.

Review Article Open Access

What role do long-noncoding RNAs play in the pathogenesis of endometriosis-associated ovarian carcinoma (EAOC)?

Alison Finall MB, BCh, FRCPath, MSc (Genomic Med)

This literature review examines evidence regarding pathogenesis of endometriosis-associated adenocarcinoma and focuses on the potential role of long, non-coding RNA molecules. The role of long non-coding RNA species is an area of active research and represents an opportunity for novel biomarker Identification to aid early diagnosis, risk stratification and post-operative disease monitoring.

Review Article Open Access

Breaking malignant nuclei as a non-mitotic mechanism of taxol/paclitaxel

Elizabeth R. Smith, Xiang-Xi Xu

Discovered in a large-scale screening of natural plant chemicals, Taxol/paclitaxel and the taxane family of compounds are surprisingly successful anti-cancer drugs, used in treatment of the majority of solid tumors, and especially suitable for metastatic and recurrent cancer. Paclitaxel is often used in combination with platinum agents and is administrated in a dose dense regimen to treat recurrent cancer.

Commentary Open Access

PAK1 and PAK4 as therapeutic targets for Ewing sarcoma: a commentary

Sydney E. Parks, Jason T. Yustein

Ewing sarcoma (ES) is an aggressive pediatric bone tumor that is prone to metastasis. Due to low five-year survival rates and limited therapeutic options for metastatic disease, there is a dire clinical need for improved ES treatments. Targeting p21-activated kinases (PAKs) may be key. PAK1 and PAK4 are associated with aggressive ES and poor patient outcomes, although their molecular mechanisms remain largely uncharacterized in this disease.

Commentary Open Access

Combination immunotherapy: The new roadmap for the treatment of intrahepatic cholangiocarcinoma

Anna S. Tocheva, Sara E. Young, Daniela Sia

Intrahepatic cholangiocarcinoma (iCCA) is a catastrophic malignancy of the intrahepatic bile ducts and one of the neoplasms with incidence rates that have been rising faster than almost any other cancer. This steady increase combined with the high mortality rates underscore the fact that optimal management of iCCA remains a challenge. While immune checkpoint inhibitors (ICIs) as single agents have elicited discouraging results in patients with iCCA, the combination of chemotherapy plus anti-PD-L1 blockade has recently 

Case Study Open Access

Correlation between marker profiles of tumor tissue and circulating tumor cells in a Grade 3 colonic neuroendocrine carcinoma: Case study and review

Agnes Michalczyk, Abhirami Venugopal, Sonia Yip, Shu Fen Wong, Mustafa Khasraw, M Leigh Ackland

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that occur in many organs. The routinely used IHC markers for NEN diagnosis include chromogranin A (CgA), synaptophysin, Ki67 and CD56. These markers have limitations including a lack of correlation to clinical outcomes and their presence in non-tumor tissue. Identification of additional markers in NEN tissue has the potential to improve clinical outcomes. We generated a detailed tumor profile of tissue from a patient with a grade 3 colonic NEC using phenotypic cancer markers and correlated this with the marker expression of the corresponding patient circulating tumor cells.

Commentary Open Access

Signaling disruptions in NK cells in patients with cancer

Gulnur K. Zakiryanova, Michael R. Shurin

Dysregulated functioning of the immune system is an important part of carcinogenesis and understanding the mechanisms of immune defects can lead to significant improvements of cancer treatments. We have first evaluated molecular defects in lymphoid cells, including NK and T cells, isolated from healthy donors and cancer patients by assessing expression of key molecular regulators, such as c-Myc, Notch1, Notch2, p-53, Cdk6 and Rb. Our results revealed a reduced expression of the proto-oncogene c-myc and Notch1 signaling in the immune cells in patients with cancer. 

Commentary Open Access

Pyscho-oncological considerations for indigenous populations

Sneha Sethi, Xiangqun Ju, Joanne Hedges, Lisa Jamieson

Cancer is one of the most dreaded diagnosis, with significant impact on the patient, carer and family. The diagnosis can lead to variety of emotions like confusion, anger, despair and fear. In case of Indigenous peoples, the process of sickness, disease and treatment are all closely related to connection to land, country, family and community. This paper evaluates the different responses recorded as a part of a larger Indigenous Australian study, regarding the feelings and emotions one feels when they hear of cancer (“the Big C”) in the community or family.