63 retired electrical engineer who lives in Durham N. Molecular Medicine Partners Healthcare Center for Personalized Genetic Medicine experienced just published their findings in the and in Science. But Alan didn‘t know that at the time. After recovering from pneumonia contracted a couple of years earlier his doctor spotted a shadow on a lung X-ray. Rabbit Polyclonal to AKT1 (phospho-Thr308). A definitive diagnosis required a needle biopsy so at his family’s suggestion Alan drove to Massachusetts General Hospital – another stroke of good luck. In fact one of the physicians around the hospital’s EGFR mutation research team was head of thoracic oncology when Alan began his gefitinib regimen. Lecia V. Sequist MD MPH “I started on Iressa on Thanksgiving Day and it was just amazing ” Alan recalls. “Literally within days my symptoms disappeared – cough shortness of breath those kinds of things. I noticed a difference Navitoclax almost immediately. ” A couple of months later CAT scans showed a dramatic reduction in the tumors. More than six years later Alan remains on treatment and feels very well with long-term disease control. Not bad for someone whose initial diagnosis gave him less than a 12 months to live. Good news The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib (Tarceva) had been widely used in clinical trials in the United States but it wasn’t until 2004 that the link between the EGFR mutation and therapeutic response to these two TKIs became obvious. Good news but only for the subset of non-small-cell lung carcinoma (NSCLC) patients like Alan whose tumor tissue assessments positive for the mutation. For those who test negative the standard of care for NSCLC is still chemotherapy. Alan now sees thoracic oncologist Lecia V. Sequist MD MPH every three months for any CAT scan and checkup. Sequist is assistant professor of medicine at Harvard Medical Navitoclax School and a faculty member at the Center for Thoracic Cancers at Massachusetts General Hospital Cancer Center. “Until six years ago the treatment for lung malignancy was fairly cookbook ” Sequist says. “It wasn’t personalized at all. Several kinds of chemotherapy were available. They all had modest activity and also you went through them in an algorithmic fashion to try to prolong people’s lives. The success was actual but marginal.” In a multicenter trial that Sequist and colleagues around the country merged shortly after the EGFR mutation was discovered 55 percent of patients with the mutation responded to gefitinib and common progression-free survival (PFS) was 12 months. With standard-of-care chemotherapy the response rate is usually 20 to 30 percent and average PFS is three months. Because gefitinib and erlotinib come in tablet form they also eliminate the time expense and inconvenience of infused chemotherapy. The label for gefitinib includes diarrhea rash acne and dry skin among adverse reactions but Alan doesn’t consider the rash he experiences with his daily 250-mg regimen a problem. “On regular chemo Navitoclax you’ve got pages of side effects but there’s very little to talk about here.” Both the National Comprehensive Malignancy Center and the American Society of Clinical Oncology now include EGFR screening and first-line monotherapy with gefinitinib or erlotinib in their NSCLC practice guidelines. Driver mutations Regrettably neither erlotinib nor Navitoclax gefitinib cures NSCLC which accounts for 90 percent of all lung cancers. And over time the malignancy develops resistance to these drugs. Sequist and other researchers are trying to determine why these cancers become resistant to these medications so that resistance can be prevented or delayed. The fact that personalized drugs like gefitinib and erlotinib eventually lose their effectiveness suggests that somatic cell genes continue to mutate. That’s why Navitoclax one tumor biopsy early in the history of the disease may not be enough. “A lot can change in the biology and the different genetic markers that we find on repeat biopsies after patients acquire resistance to certain drugs that they were in the beginning sensitive to ” Sequist reports. “Our concept of what malignancy is and how.