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Gene Therapies Vs. Cancer: Insights from an Industry Leader

Gene Therapies Vs. Cancer: Insights From an Industry Leader

PerkinElmer recently discussed next-generation cancer therapies with one of the founders of the field, Dr. Sunil Chada.

The complexity of cancer continues to pose significant challenges for researchers in the development of novel therapeutic agents. Historic treatment approaches including chemotherapy, radiation, and immunotherapies such as antibody therapies have failed to deliver curative outcomes for most patients due to cancer resurgence. The current standard of treatment is focused on combating tumorigenesis on multiple fronts by combining chemotherapies with immunotherapies. Outcome measures have improved substantially over the past three decades. However, further development is needed to shift the paradigm from treatment to cure.

Antibody monotherapies have been well researched, and currently hold marketing approval for 93 products, with more in late-phase clinical research or awaiting regulatory review. Antibody and cytokine therapies treat cancer at a more localized level than chemotherapies, and work with the body’s immune system to identify damaged cells and remove them via endogenous cellular processes.

Broadening the research perspective

The difficulty in antibody and cytokine therapies is one of specificity and selectivity. Not all types of cancer exhibit biomarkers that can be targeted with antibody and cytokine therapeutics. If a certain type of cancer exhibits an overt expression of a biomarker, for example PD-L1, an antibody against that marker, anti-PD-1, can be administered with the goal of turning on endogenous cytotoxic-mediated immune responses specific to cancer cells. Broadening the research perspective to cell and gene therapies offers an alternative pathway to potential treatment options.

Cell therapy involves the transfer of cells to a patient for the purpose of therapeutic intervention. A lack of novel biomarkers expressed specifically in cancer cells while not in normal healthy cells is a limiting factor in the feasibility of cell therapy. CAR-T cell therapy represents a substantial portion of cell therapy research, and has the goal of using a patient’s own cells to generate a robust immune response specific to cancer. With clinical success and limited approval, CAR-T cell therapy has offered substantial improvement as compared to standard therapies in select types of cancer.

Tumor suppressor gene therapies and CRISPR

Gene therapies focus on treating cancer at the genetic level, with gene mutation and aberrant protein expression being the target of intervention. There are multiple avenues of which to approach gene therapy, each presenting a different challenge in navigation due to the complexity of cellular processes involved. Tumor suppressor gene therapies, including p53, are under investigation as a means of using endogenous mechanisms to fix broken or mutated DNA which collectively gives rise to cancer. Cancer’s ability to mutate and turn off immunosurveillance mechanisms allows for uncontrolled growth, division, and evasion.

Gene editing techniques have been investigated for the treatment of cancer, with CRISPR offering a mechanism of isolating, editing, and altering genes therefore selectively fixing mutations which give rise to disease. Advancements in scientific technologies such as genomics, proteomics, and machine learning combined with evolving research and conceptual understanding of the intricate processes involved in carcinogenesis is slowly shifting the treatment paradigm from treatment to cure.

Please download our whitepaper that goes into granular detail on these promising developments.

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