Journal of Cancer Biology

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

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.

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.

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.

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.

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.