Precision Medicine 101: Out of the Lab and into the Clinic: Translational medicine becomes personal.

Often capitalizing on the differences between one cancer and the next has provided the greatest strides achieved against certain cancers. The paradigm successes of modern oncology are built on the bedrock of defining these differences and the genomic technologies that allows us to do so. In the old controversy between the lumpers and the splitters, the splitters have it. The lumpers who prefer simplicity and reductionist approaches to disease are ill-suited for careers in oncology, and the lumpers in practice are for the most part unhappy and overwhelmed by the explosive growth of genomic insights, and the ever-greater complexity of patient management. But there is no stopping the Niagra - previously unknown drivers create new therapeutic possibilities for patients and lead to historically unprecedented outcomes in controlling cancer and improving survival.

The heterogeneity among patients with a given cancer poses steep new challenges to the study and treatment of the disease. For example, the uncommon subtypes of a common disease such as lung cancer amounts to a group of many rare or uncommon conditions. This makes it harder to test new treatment hypotheses. Even more challengingly, mutations in one part of a gene may confer responsiveness to a given drug, but in another part of the same gene, a different mutation generates no benefit at all. The explosion of new insights also creates new challenges for physicians to remain abreast in the field. Not least, the old business model of giving everyone the same drugs to generate huge profits for the pharmaceutical industry is also in need of change to a business model where profits can be developed from developing drugs in a group of smaller but far more numerous niche markets. No less, the regulatory hurdle of drug approval is still chained to the past and could evolve much more quickly into approving molecular indications rather than disease site indications. Just as the laws of physics are the same everywhere, pathway aberrations across multiple cancers tend to be pathogenic wherever they are found with relatively few caveats. Is it really cost effective to test the same treatment hypothesis in 40 different disease types once the drug is on the market? Not least of all, the refusal of the insurance industry to pay for molecular diagnostics and off-label drug use for agents identified in the course of profiling a patient’s cancer is not only a tragedy of denying access to lifesaving treatments for the patient, but one of the great recalcitrant, shortsighted, and inefficient (shall we stay bluntly - stupid) uses of resources of our time. It is not that precision medicine will only add to the cost of care; it will eliminate an enormous amount of ineffective and outrageously expensive drugs in patients that cannot benefit from them. All these challenges create terrific resistance to and inertia for the development of precision medicine.

Nevertheless, the time has emerged, when we can peer into a particular cancer’s molecular underpinnings and see precisely what is going on. The standard of care in oncology if not all of medicine is an evolving historical process, informed by discovery and treatment breakthroughs, but never beyond critique of its intrinsic limitations.

In oncology, the standard of care has been based mostly on marginal improvements evolved with a molecular blindfold. We now have the option to embrace the historical moment with every patient we see to identify the molecular Achilles heel lurking in their cancer, or the resistance pathway we may be able to do something about.