No two cancers are exactly the same and while precision oncology has led to dramatic improvements in many areas, specialists are only just beginning to unravel why some patients with the same molecular signals do not respond the same way or develop resistance over time to targeted treatments. Much of this uncertainty will eventually become known through research and clinical practice, but for now precision in many respects is cancer care as an art form more than a technical certainty.
Despite significant advances for the past twenty to thirty years in precision oncology and the rapidly changing standards of care for different cancers, there are still large gaps in the ability of cancer specialists to identify genomic variants and connect them with other factors to determine exactly how these molecular differences affect a person’s cancer. For instance, the US FDA has approved over thirty kinds of immunotherapies for patients with various forms of cancer, but still for many patients their tumors do not respond to these treatments or their cancer develops resistance to the therapy. Developing resistance remains a central issue in the use of most targeted cancer therapies.
Most cancers have a number of mutations of unknown effect and many experts caution about making treatment and management decisions based only on molecular testing. The ability to meaningfully interpret molecular test results and match them to a treatment and management strategy most likely to succeed is more times than not a complicated undertaking even in well-resourced settings. In lower-resource settings, additional factors make it much more difficult. A recent study from India showed that only 8 percent of a few hundred cancer patients with comprehensive genetic profiling actually received targeted therapy and that only half of that small percentage derived clinically meaningful benefit (Ref: JCO India CGP Editorial).
Even a supposedly good match between a molecular signature and a targeted medicine does not lead to success in all cases. Specialists many times achieve different outcomes even when two patients have the same molecular information and the same cancer type, or a tumor in a different part of the body with the same molecular behavior as a tumor elsewhere may not respond the same to the indicated medicine. Furthermore, overall side effects from targeted approaches may be less severe than traditional cancer treatments, but they do occur and, importantly, cancer specialists are less knowledgeable about why they occur given that many forms of precision oncology are new.
The bottom line is that cancer remains extremely complex and not all patient needs will be sufficiently met by current forms of precision. Specialists will be the first to say that understanding the underlying molecular mechanisms of any one person’s cancer for precision therapy to be possible and successful still has a very long road to travel.
