Understanding the Complexities of Cancer and Progress in Personalized Medicine

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Personalized cancer care holds much promise; it gives us confidence that targeted treatments will eliminate cancers and spare us the one-size-fits-all cancer treatments of our past. For the sake of simplicity, we want to think of personalized cancer care as a lock and key; each tumor has a specific puzzle interface, and when the puzzle piece is identified then the cancer melts. This simple message of “lock and key” is comforting because it suggests that we can achieve a new reality where we assess a tumor and choose a treatment in a very simple way, based on a tumor’s genetic makeup.

We have many exciting new targeted cancer treatments in our toolbox – consider, crizontinib (Xalkori®) for non-small cell lung cancer and vemurafenib (Zelboraf®) for BRAF mutation-positive metastatic melanoma. These therapies have been effective in patients with specific gene mutations. At the same time, as the science advances, research continues to reveal the underlying complexities of cancer and the diversity of tumors.

In the March 8 issue of The New England Journal of Medicine, the authors of “Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing” provide an exquisite roadmap of how heterogeneous and complex one individual’s cancer can be with many mutations lurking within each tumor mass, and the mutations themselves evolving over time. The picture presented by Gerlinger and colleagues, suggests the need for many keys to a myriad of locks, each tailored for a particular tumor at a particular point in time. The simple message of lock-and-key personalized medicine, where simple one-to-one decisions can be achieved, would not hold true.

This may create concern that a personalized medicine approach has created a false sense of hope. I don’t think that it is false hope, but rather a false sense of the simplicity.

There is hope. While a single needle biopsy may not create a complete picture of a cancer, biopsies are still a crucial part of characterizing tumors, using growing scientific knowledge to understand which treatments might work best. Biopsies are a starting point. A number of institutions are conducting genetic and genomic analyses on tumors. This is probably not the Holy Grail, but rather an iterative step in a long trail of scientific advances that will support personalization of cancer medicine.

In addition, new technologies are needed to improve on the information gathered, including methods to understand whole tumor heterogeneity. If we believe a personalized approach is simple, we are at risk of not building the systems needed to deal with the deluge of complex information that will need to be sorted, understood, and applied clinically in real time.

We need both the science and the information technology solutions to keep improving. New understandings highlight new opportunities to target more central cancer mutations, and to create more thoughtful treatment cocktails.

The underlying message here is that although we have made great progress, we are still early in our journey. In reality, this is a very comforting message. It would be disheartening if we had already exhausted the targeted treatment toolbox and that the best we could achieve is delayed cancer progression but not cures. By embracing the complexity of more individualized information for any particular patient and tumor, we really do have the hope of achieving personalized cancer care.

As we uncover new and unimagined pathways during the scientific discovery process, we should not be deterred or disheartened. We just aren’t there yet. We need to ensure that public policies support the continued investment of energy, attention to detail and resources required to achieve a vision for personalized cancer care.

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