After just returning from the 2016 American Society of Clinical Oncology meeting in Chicago, it was clear that there is a palpable excitement over recent progress in cancer research and therapeutic drug development.
Howard Kaufman, MD, FACS
After just returning from the 2016 American Society of Clinical Oncology (ASCO) meeting in Chicago, it was clear that there is a palpable excitement over recent progress in cancer research and therapeutic drug development. This was evident as we heard about the expansion of immunotherapy into more diseases, including bladder, head and neck, Hodgkin’s lymphoma, AML, CLL, multiple myeloma and even Merkel cell carcinoma. In addition, significant insights are emerging on how resistance develops in patients on targeted therapy with new ideas for overcoming drug resistance. The excitement, however, was tempered by the high profile appearance of U.S. Vice-President Joe Biden, who applauded our progress but warned that expectations are not very high and we must deliver on the promise. This made me wonder, is cancer indeed a curable disease, or only one that can be controlled for a limited duration?
Cancer has been characterized as a genomic disease. This paradigm has been extremely useful for understanding both the nature of neoplastic transformation, tumor progression and metastasis as well as for diagnostic and therapeutic approaches to disease management. While the inherent instability of the tumor cell genome is now well established, we also understand that tumors develop in the context of a particular microenvironment and in the face of the host immune system. This recognition has provided new clues into the natural history of certain cancers and resulted in new targets for therapeutic intervention. Another way to consider cancer is in the interaction between an evolving malignant cell and the emergence of host anti-tumor responses, including metabolic adaptions, alterations in blood flow and local physiology and induction of anti-tumor immunity. This paradigm suggests that there is a dynamic interaction between tumor evolution and the host’s ability to evolve rapidly enough to contain or eradicate newly evolved tumor cell clones.
So what does this form of thinking tell us? On one hand, game theory would suggest that cancer will not ever be truly curable we may hold it off but because there is evolution on both sides, once started it cannot be completely stopped. Game theory is a new mathematical approach that has been applied to situations of conflict where there are two or more decision-making bodies. In general, game theory has been used in helping predict outcomes applied to politics, public policy, economics, and psychology. Further research is needed to understand if game theory can be applied accurately to biologic systems. Further pessimism for cancer “cure” can be extrapolated from the increasingly rapid rate of tumor cell genetic instability, and hence cancer heterogeneity while other systems, such as the immune response may evolve much more slowly. Clinical observation also tells us that many cancer patients can develop recurrences often many years after an apparent “complete response.” So, what data support the supposition that cancer is curable?
My particular area of interest has been in immunotherapy and it is clear that in admittedly awed — animal models, cancer can often be eradicated with hosts exhibiting subsequent immunity to tumor challenge. In addition, there are many anecdotal reports of patients with complete responses to immunotherapy that remain alive and free of disease 1520 years after treatment. These observations are intriguing but do not prove that patients can be cured. Perhaps the most compelling argument to be made that cancer might be curable comes from studies of vaccination against infectious diseases. These studies provide compelling evidence that prophylactic treatment is associated with disease control at both the individual, and more importantly, population level. It is widely recognized that immunotherapy may be also more potent when utilized earlier in the natural history of the disease, or even before malignant transformation occurs. The translation of new therapeutic approaches in both targeted and immunotherapy to the adjuvant and prevention settings is only just beginning. Thus, further research is needed to better define whether cancer can truly be ‘cured.’
We are living through a historic time in biomedical research with advances on many levels. Now is not the time to become complacent, but rather now is the time to increase research funding, refer patients for clinical trial participation, and engage the full scientific and clinical community in the war against cancer. Fifty years ago we did not consider cancer a genomic disease and travel to the moon was considered marginally possible. Today, we are planning to send humans to Mars and oncologists are writing editorials on whether cancer is potentially curable.