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  • Writer's pictureKirk Hartley

Genomics and New Gene Fusions Found in Some Non Smokers With Lung Cancers

As lung cancer claims flood into asbestos litigation, one wonders if more attention will be paid to genomics by insurers, former sellers of ACM, trustees of asbestos trusts, and futures representatives. On that subject, consider this article from a talk at Davos by the president of Foundation Medicine. The cost of the test has not yet been settled, but the company’s SEC filings indicate it has sold many tests for less than $5,000. The company is one of the leaders in sequencing genes to understands the drivers of cancer. His speech highlights a new gene fusion found as the driver of lung cancer in four non-smokers:

"The very first clinical case profiled at my company, Foundation Medicine, was a non-smoking male in his early 40s, diagnosed with lung cancer. When his tumour was analysed, a new gene fusion that was driving the growth of his cancer was discovered. Working in collaboration with colleagues at the Dana Farber Cancer Institute in Boston, Foundation Medicine showed that a certain class of drugs called RET inhibitors, which had already been approved by the FDA for diseases including kidney cancer and gastrointestinal stromal tumours, showed activity in cancers with this type of alteration. This finding was quickly published in the journal Nature Medicine in February 2012.

Several months later, another patient was found to have a similar gene fusion. She was enrolled in a trial for an RET inhibitor and within one month, her tumour showed significant shrinkage. This response, and those of two other patients enrolled in the trial, was published in the journal Cancer Discovery in March 2013. This speed of target discovery to demonstrated patient response is unprecedented in drug development history.

Medical science is accelerating at a pace never before seen in human history. Rapid advances in genomic sequencing are revolutionizing the way scientists search for and discover the mechanisms of disease, potentially transforming research, therapeutic development and clinical care. Nowhere is this more evident than in the field of oncology, where we can now understand each patient’s cancer at the level of its molecular blueprint.

While cancers are still treated based on where they are found in the body, we now know that they are more accurately categorized by the underlying defects in the DNA (or genomic alterations) that drive cancer growth, which can be targeted to personalize a patient’s treatment, often regardless of the type of tumour.

We are quickly learning more about the genes linked to cancer, as well as the drugs that may target them. In parallel, we are learning about mechanisms of resistance to these drugs, which can be used to more precisely target therapy. This would have the effect of transforming many cancers into chronic diseases – or even finding a cure.

Today, the technology exists to routinely profile individual patients’ cancers, enabling physicians to target the tumour with therapies that can control and potentially eradicate the cancer, realizing the promise of precision medicine for many. But with these advances come great challenges. What does a doctor do with the information? How does a doctor choose among several targets? How do we choose a treatment for a patient when there is little or no published clinical evidence for a given tumour type? It is impossible for a practicing physician to keep up with the explosion in knowledge, and the existing paradigm of population-based clinical trials is far too slow to keep pace with a field that is moving towards individualized treatments.

Information technology must be the key enabler. Information exchange across the global cancer community is critical for success in the fight against the disease, allowing physicians to easily access, share and analyse genomic and clinical data to help inform treatment decisions. When genomic information for a given patient is combined with information about their clinical history, and mined along with thousands of other patients, patterns may be discerned that could guide treatment. Technology will allow us to incorporate what we learn every day in clinical experience into our collective knowledge and accelerate the move towards precision medicine.

I imagine a future in which every patient with cancer can have their tumour analysed in a comprehensive fashion, whether they are being treated at a major cancer centre or in a rural community practice; a future in which oncologists and their patients benefit from the knowledge gained from each patient before them; a future in which each patient’s clinical data is integrated into a larger knowledge base with other real world data, aggregated with the latest scientific and medical knowledge, and synthesised to inform real-time decision-making, ensuring that each patient’s treatment is informed by a deep understanding of the genomic and other molecular changes that contribute to their disease.

Author: Michael Pellini is chief executive officer and president of Foundation Medicine and is participating at the World Economic Forum’s Annual Meeting 2014 in Davos."


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