Taking Aim

By translating research into targeted therapies, our physician-scientists are exploring a new generation of drugs that target cancer-causing mutations across multiple tumor types

Learn more about molecular fingerprinting “Patients whose tumors harbor specific mutations can be directed to new therapies – typically pills – which target their tumors much more effectively and with fewer side effects.”- Alice Shaw, MD, PhD

Taking aim

Translating research into targeted therapiesTraditionally the first step in cancer treatment was determining where the disease began. Once the location was known, lung cancer was treated with lung cancer drugs, breast cancer was treated with breast cancer drugs, and so on. But that paradigm is changing to a new approach known as personalized cancer care, which uses a new generation of drugs that target cancer-causing mutations across multiple tumor types. These new targeted drugs require a new method of diagnosis - the molecular fingerprint – an analysis of the tumor’s genetic changes.

Molecular Fingerprinting Obtaining molecular fingerprints has been a cumbersome process used on only a few patient tumors, but the Mass General Cancer Center now has developed a unique and highly automated method for extracting the necessary genetic material and analyzing it gene by gene. The robotic equipment, purchased with the support of Aid for Cancer Research, is so efficient that the Cancer Center expects to routinely profile the tumors of each of the 7,000 new patients seen annually by the end of this year. Unlike other centers, which generally test only for the mutations most commonly associated with a particular tumor, the Mass General Cancer Center aims to test all tumors for a large variety of cancer-causing mutations – currently a total of 122 mutations on 15 genes. The equipment is scalable to accommodate new cancer gene mutations.

“Genetic testing is assuming an increasingly important role in the care of select patients with lung cancer,” says Alice Shaw, MD, PhD, a Cancer Center oncologist. “Patients whose tumors harbor specific mutations can be directed to new therapies – typically pills – which target their tumors much more effectively and with fewer side effects.” The Cancer Center began routine testing with lung cancer patients, and has expanded in the last 12 months to other tumor types.

Benefits for current and future patients The benefits of molecular fingerprinting go beyond today’s cancer patients. The Mass General Cancer Center is building a storehouse of information on mutations collected from its screening process that can be combined with anonymous data on treatment success, which will be used by researchers looking for new targets or ways to improve existing drugs. This information will help uncover potential targets for new drugs, speed promising drugs into clinical use, and reveal ways to make approved targeted drugs more effective.

One example of these benefits is providing new options for a patient whose tumor has become resistant to therapy. “Traditional chemotherapy had so many effects in a cell that scientists understood very little about how tumors became resistant,” explains Leif Ellisen, MD, PhD, an oncologist who, along with A. John Iafrate, MD, PhD, directs the Molecular Pathology Translational Research Lab where tumor profiling is performed. “With targeted drugs, resistance to therapy is much more specific.” In lung cancer patients, for example, an acquired resistance to one targeted drug is commonly caused by the same secondary mutation. Armed with that knowledge, Cancer Center scientists have begun developing drugs aimed at the secondary mutation.

This totally novel approach to diagnosing and treating cancer, says Iafrate, “gives our oncologists more information about a patient’s cancer so they can treat it in a very specific way, thereby significantly increasing the odds of success.”

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