Precision oncology promises a new model of cancer care where medical decisions are based on a holistic view of the patient, including their genes, environment, and lifestyle, and tailored to the molecular profile of their tumor. To date, great strides toward the paradigm of precision oncology have been made in the area of cancer immunotherapy, which boosts a patient’s own immunity to combat tumor cells. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapies have dramatically improved outcomes for a select number of patients, but widespread use of these treatments remains elusive.
To make personalized cancer treatment a reality for all patients, we need to reimagine the biopharmaceutical business model and drug development process, both of which have traditionally been focused on broad drug development and blockbuster drugs. New regulatory, technical, clinical, and economic frameworks are needed to ensure that the right patient can access the right therapy in a meaningful timeframe. In this article, I discuss three key challenges which must be addressed to fulfill the promise of precision oncology.
#1 Understanding and addressing mechanisms of resistance
The ultimate goal of cancer immunotherapy is to stimulate the immune system to launch a sustained attack against tumor cells. Given the complex and dynamic interactions between tumors and the immune system, achieving this is complicated. The challenge lies in managing the delicate balance between autoimmunity and the immune system’s ability to recognize non-self. In some cases, the immune system may fail to recognize tumor cells as non-self and may develop a tolerance to them. Moreover, tumors have myriad methods for evading the immune system (see Figure 1).Resistance to cancer immunotherapy can be categorized as primary (i.e., failure to respond) or secondary (i.e., relapse after successful treatment). Approaches for optimizing response and minimizing resistance to cancer immunotherapies include developing biomarkers to assist with patient selection or treatment monitoring, altering the tumor microenvironment, and educating healthcare practitioners on the potential for delayed response with these types of treatments. With CAR-T therapies, resistance may be due to poor persistence of CAR T-cells after infusion or due to antigen loss of the target receptor.