Cancer Immunotherapy Could Be Boosted by Targeting Pathways of DNA Repair

A newly published study shows that the fight against cancer could be boosted by considering approaches that seek to disrupt the mechanisms through which tumor cells respond to damage to their DNA. Targeting these pathways could make immunotherapy more effective for a lot more people. 

The study team led by Tang Z. focused on DDR (DNA Damage Response), a process at the cellular level in which cells undertake a variety of measures to fix any damage to their DNA. This repair process is intended to keep the tumor functioning and able to continue growing and spreading. By disrupting DDR, cancer cells can become more vulnerable to being targeted by the immune system and treatment modalities like immunotherapy. 

DDR helps tumors to thrive, but at the same time, the DDR process offers a potential vulnerability that can be exploited to stop cancer in its tracks. 

The researchers reviewed several studies that are ongoing or have been completed exploring how DDR inhibitors are being combined with immune checkpoint therapies in different cancer types, such as breast, ovarian and lung cancers. These studies show that treatment responses can notably improve when such novel approaches are taken. 

The study team emphasizes that resistance mechanisms and toxicity profiles need to be studied further before this new approach to cancer treatment can be moved from the lab to the bedside in hospitals. 

Tang and his team say that, while seeking to disrupt tumor DDR processes promises to weaken cancer and make malignant cells easier to attack, the same approach carries the risk that normal cells in a patient could also be damaged and there is a possibility that systemic inflammation could be triggered. It is therefore important for additional studies to be conducted so that adverse effects on the patients can be minimized while exerting maximum damage to tumor cells. 

The research team also points out that tumor cells are well known for quickly mutating in order to sidestep any barriers that they encounter in their bid to grow and spread. Consequently, there is a high possibility that tumors could activate other pathways to repair their DNA once the known DDR processes are disrupted. For this reason, the treatments used need to be combined with real-time monitoring of cellular processes so that needed adjustments can be made in time as the molecular response in patients requires. 

Many technologies, such as proteomic and advanced genomic testing are invaluable if therapies targeting DDR are to be successfully combined with immunotherapy. Precision oncology can advance to the next level as these cutting-edge molecular monitoring technologies are incorporated in guiding treatment dosage and patient selection. 

As the use of DDR-targeting therapies is further studied, other approaches, such as the use of oncolytic virus treatments, are also being studied by companies like Calidi Biotherapeutics Inc. (NYSE American: CLDI). The fight against cancer is at an inflection point, and major breakthroughs offer hope to patients diagnosed with various malignancies. 

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