The Time Is Right for True Precision Medicine in Oncology

Andre Goy, MD

In his State of the Union Address in January, President Obama announced a new national precision medicine initiative. This initiative would focus on oncology in the near term, while expanding this approach of “customized and rationale-based medicine” at large in the long run. Practically, the effort would involve a million American volunteers who would “further the development of personalized, genetics-based medical treatments.”

This is obviously encouraging and perfect timing given the changes happening in medicine, as I often allude to in these columns. On the other hand, as expected, the president’s announcement also generated a lot of skepticism, from the relatively small amount of support ($215M total to map out specialized treatments based on patients’ and healthy individuals’ genetic profiles), to the unrealistic goals represented by the advocates of personalized and precision medicine. Some even talk about the hype around personalized medicine and make the parallel with the declaration of “War on Cancer” by Richard Nixon in 1973, which didn’t live up to the hype it generated.

Clinically, experts don’t even agree on a single term for the approach. We hear the terms individualized, personalized, and precision medicine often used interchangeably. Everyone would agree, however, that the “one-size-fits-all blockbuster drugs/approach” is over.

The basic concept of personalized medicine is not new— from blood typing for transfusions, to observation of slow versus fast metabolizers of antibiotics during the TB era, to today’s examples, including the adjustment of medication, such as coumadin, based on enzymes polymorphisms (eg, CYP2C9) that affect/reduce enzyme activity and lower clearance rates of warfarin. Oncology is at the vanguard of this revolution, already using a number of biomarkers to decide on therapy, such as molecular markers in breast cancer (eg, ONCOTYPE), or even replace chemotherapy in some situations, such as with the EGFR mutants story in lung cancer—those who respond to kinase inhibitors (eg, erlotinib or gefi¬tinib) better and with less toxicity than chemotherapy. Indeed, lung cancer now has at least 11 mutations that affect treatment recommendations. Key elements of this paradigm shift originated in hematological malig¬nancies, particularly with lymphomas and leukemias.

Thus, the timing is right for oncology to become the first truly personalized medicine, from the availability of technology at a lower price (whole genome DNA se¬quencing is currently <$1000), to the ability to handle big data (bioinformatics), to the number of new drugs (mostly targeted biologics) in oncology (with >70% of the entire pipeline of medicine). Over the last few years, the acceleration in the field is actually palpable, and will lead to a new taxonomy of cancer (see my previ¬ous column “A Revolution in Classifying Cancer?” at http://bit.ly/Goy_OBTN_Aug14). However, there are also a number of emerging challenges to address in order for this ongoing revolution to be successful.

First, the complexity of the landscape is daunting, from factors associated with the tumor (genomic di¬versity and clonal heterogeneity), to factors associated with the host (SNPs associated with cancer risk, differences in drugs metabolism, or reaction to the tumor itself with the microenvironment), to proteomics of the tumor cells and immune cells (cytokines), just to name a few.

Establishing relevant signatures that can be used in the clinic will require a global endeavor, including changes at the government level to adjust the regula¬tory frameworks. In particular, regulatory changes are needed to support innovative trial designs (molecularly relevant small trials with approved and validated com¬panion diagnostic tests) and for obtaining patient consent to access materials (biopsies and medical records— still a huge issue these days). The technology continues to evolve very fast, from big data handling to the ability to analyze circulating tumor cells or naked DNA (liquid biopsies), or even all subtypes of immune cells in one small drop of blood.

Oncology could lead the field in medicine to transform care delivery. This is not just an academic endeavor, but also the only solution to address the unsustainable cost of medicine, particularly cancer care. If we embrace the future, we could develop new ways to develop drugs, better stratify patients, and diagnose patients earlier. Similarly, enforcing goals of minimal residual disease in cancer (not only in hematological malignancies) will help customize costly maintenance therapies.

Bioinformatics platforms are needed to create a dashboard to help physicians’ decisions. We have developed COTA (cancer outcome tracking analysis system) that has created more than 500,000 nodal addresses across all cancers, allowing us to stratify patients based on clinical and molecular features in order to be able to fol¬low and predict their outcome while containing cost— smarter medicine is better medicine.

And so, precision medicine has arrived in oncology, but challenges remain before we see its true potential realized. Patients are ready, they deserve it, and we need to all cooperate as partners toward innovation to radically reinvent the way we deliver cancer care in the near future.