Information, innovations and health care:
a plan for presonalizing progress
Updated - 2017
We are all connected to our computers (that is, iPhones) on a daily basis and, beyond politics and disasters, much of what captivates us is news about therapeutic innovations. As we watch television, we are exposed to news about recent breakthroughs and discoveries – many ready to be prescribed despite a litany of side effects, because of new and heretofore unachievable benefits. Cancer treatment in recent years has captured much of the lay public’s attention.
The initial therapies targeted particular oncogenes directly implicated in tumor growth, such as imatinib (Gleevec) directed to the ubiquitous bcr/abl in chronic myeloid leukemia, or Herceptin – an antibody directed to the erbB2 receptor amplification that accelerates the growth of Her2 over- expressed breast cancers. Following these initial successes other cell signaling pathways were targeted, but key patient selection most likely to benefit from inhibiting predominating tyrosine kinases proved to be considerably more complex. Nonetheless, patients with metastatic
kidney cancers clearly benefited from drugs such as sorafenib, sunitinib, pazopanib, lenvatinib, vendatinib, carbozertinib and other multi-targeted small molecules that also were shown to be efficacious to a variable degree against some types of sarcomas and thyroid cancers. The next wave of enthusiasm over novel therapies related to unleashing of the immune system, which was covered in my report last year, that stressed in addition the possible promise of prevention. This field has continued to develop at an unparalleled pace, and we are seeing immunotherapy impart benefits to patients with a number of cancers that are or had become refractory.
Much of the success of these treatments and their implementation rely on innovations fueled by ever increasing costs that are justified for continued drug development. All of this focus on drug development, however, obscures the impact of these strides in health care and their potential beyond their initial indication based on clinical trials data. Pharmaceutical industries, perhaps learning from the AIDS clamor in the 1980s, have made their new drugs available in certain instances for “off-label” treatments or as an expanded access. As a physician in an academic center and participant in clinical trials, I am keenly aware of some of the potential benefits from such treatments, but wonder whether we can harness our academic expertise to extend treatments to our patients beyond what is a reactive attitude to failure of prior treatments. With Associate Medical Directors of The Chemotherapy Foundation, we shall engage in discussion on how to introduce genomic-directed care to our patients going beyond what qualifies them for clinical trials or predictions from each individual institution testing on tumors.
Many cancer centers have been grappling with how to get the most information from a tissue specimen that often is the first step to establish the diagnosis of a new cancer or a recurrence in somebody who has already undergone treatments with the expectation of cure. As I attend local lectures or national and international meetings, a common theme of (Molecular) Pathology departments is the integration of a cancer diagnosis with a growing body of histochemical (tissue staining) features to better characterize the site of origin of the tumor (that is not infrequently in doubt) and particular subtypes.
If treatment beyond surgery is needed or even predicted to eventually be needed over time, then increasingly one reaches to extensive identification of the genome by research companies or developed in-house by major academic institutions, such as the IMPACT analysis that was set up at Memorial Sloan-Kettering dating back several years. The information obtained can be helpful in several ways: (1) To identify occasionally actionable, such as EGFR mutations often found in lung cancers that yield to tyrosine kinase inhibitors, or in BRCA acquired or inherited mutations that predict for response to DNA damaging agents or PARP inhibitors. (2) To anticipate therapeutic challenges, such as establishing that kras is mutated – a difficult feature predicting for resistance to many of our agents. (3) Generate ideas when the tumor is not being controlled by our standard approaches.
How to garner our collective strengths in tackling the complexities of these analyses, so that we can couple them with decision making and trials in a personalized way, is the challenge for current and future oncologists. Under our grant support, several grantees acquire great expertise on the molecular heterogeneity of the more difficult to treat cancers. Patients afflicted with major cancers within our area can benefit from having a conserted effort at analyzing results from genomic studies, and information on clinical trials that reaches beyond our individual institutions. Such collaborative grants will be encouraged beginning the 2018-1019 cycle.
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