Each person is unique, and so is his or her cancer. Precision medicine is based on the belief that cancer treatment can be tailored to the genetic makeup of each patient’s cancer cells, and to his or her physiology and medical history. We have a long way to go before this precise, genetics-based cancer treatment can help every person with cancer, but this approach is proving to be a powerful way of attacking cancer.
By studying the cancers of thousands of patients at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, researchers are developing a deep understanding of the genomic and biologic factors that drive cancer growth, and are using this knowledge to develop better therapies. We have already identified many genetic mutations in cancer cells that are potential targets for therapy, and are working on identifying still more. And we are working closely with pharmaceutical companies to develop and test potential drugs that strike directly at these mutations.
Chief Clinical Research Officer Bruce Johnson, MD, was among those that discovered that patients with partial and complete responses to the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib have mutations in the epidermal growth factor receptor.
With precision cancer medicine, researchers and clinicians work side by side. “Systematically studying all patients allows us to identify the specific genetic weaknesses of their tumors,” says Bruce Johnson, MD, chief clinical research officer at Dana-Farber Cancer Institute. “That allows us to approach cancer treatment not only by where the tumor originates –– that is, the lung, colon, or breast, for example –– but we can break each of these tumor types down into specific subsets based on the genetic abnormalities within them.
“Our goal is to provide the most effective therapy by combining targeted agents with conventional treatments. We will also able to better anticipate complications that could be caused by a specific gene aberration.”
This approach was good news for the special education teacher who was diagnosed in 2011 with stage 4 lung cancer that had spread to her lymph nodes and produced a lesion on her hip. A DNA test indicated that her cancer contained a EGFR (epidermal growth factor receptor) mutation, a molecular subtype of cancer that is common in non-smokers. Fortunately, researchers at DF/BWCC had discovered a drug that specifically targets the EGFR mutation.
The patient participated in a clinical trial for the now-FDA approved drug Tarceva, but after 18 months her tumors began growing again. This time, DF/BWCC researchers identified a new, previously unknown resistance mutation in EFGR, T790M, that was blocking the effectiveness of Tarceva, and provided a second combination of experimental agents. Although effective for a short time, the new targeted therapy stopped the tumor growth for only a few months.
A third clinical trial, where she is being treated with a new EGFR-inhibitor referred to as AZD9291, also developed at DF/BWCC, is proving to be effective. Her tumors are shrinking and the side effects are minimal. Now retired, she continues fighting her disease with minimal side effects three years after her once-fatal diagnosis.
“Precision cancer medicine is accelerating our ability to bring basic research to our patients,” says Jeff Golden, chief of Pathology at Brigham and Women’s Hospital. “It also reverses the flow of information, and completes the circle by bringing what we learn at the bedside right back to the laboratory to keep the process of discovery going.”
