Dr. Daniel Costa awarded the 2012 LCFA/IASLC Fellowship in Translational Lung Cancer Research
Costa to study resistance to EGFR inhibitors
The Lung Cancer Foundation of America (LCFA) and the International Association for the Study of Lung Cancer (IASLC) have named Dr. Daniel Costa the 2012 recipient of the LCFA/IASLC Translational Lung Cancer Research Fellowship. The award is given to someone who seeks to make an immediate and relevant impact on cancer patient care or to interpret the results of a clinical trial from a molecular basis to help inform decisions in future clinical trials. Costa, a medical oncologist at BethIsraelDeaconessMedicalCenter and an Assistant Professor of Medicine at HarvardMedicalSchool, is hoping to do both.
His work surrounds a specific sub group of epidermal growth factor receptor (EGFR) mutations, called exon 20 insertions. Most of these mutations are not associated with radiographic or clinical responses to currently available EGFR inhibitor treatments like gefitinib and erlotinib. This means that patients who have tumors with these mutations do not receive the remarkable progression-free and overall survival conferred by EGFR inhibitors seen in other patients with tumors harboring the more common exon 19 deletion and exon 21 EGFR mutations. In fact, EGFR exon 20 insertion mutations could account for up to 5-10 percent of all EGFR mutations, therefore affecting as many as 20,000 cases of non-small cell lung cancer each year worldwide. The research will try to characterize tumors with these mutations and identify novel therapies for the unmet clinical need of patients with such tumors.
“We want to try to improve care of patients by characterizing their tumor mutations in a systematic fashion. This could help doctors know if and when they should treat patients with certain drugs and could also lay groundwork for clinical trials in a patient population,” Dr. Costa says.
Costa says he knew he wanted to be a researcher before he even became an oncologist. During his medical training, he learned of the high mortality rates in lung cancer, meeting many patients first-hand.
“I was exposed to the diversity of patients with lung cancer and made the decision to help out and try to match the burden of the disease with research and funding,” he says.
His colleagues say he’s a real physician-scientist.
“He knows both the ‘bedside to bench’ and the ‘bench to bedside’ approaches to provide his patients with better therapeutic options,” says Susumu Kobayashi, Assistant Professor of Medicine at BethIsraelDeaconessMedicalCenter and HarvardMedicalSchool.
Costa will receive $150,000 per year for up to two years. The second year of support is based on demonstrating satisfactory progress.
“I was personally ecstatic to receive the grant,” Costa says. “My research team and I are very grateful and with it this project can move forward.”
A decade ago oncologists lumped together all non-small-cell lung cancers (NSCLCs) as a single disease and treated them with similar ineffective regimens. Molecular discoveries in the last several years have made it abundantly clear that NSCLCs that look similar are molecularly diverse, and the differences from one tumor type to another are vast. In 2004, epidermal growth factor receptor (EGFR) mutations were identified in tumors from approximately 15%-20% of patients with NSCLC (more than 200,000 patients a year worldwide). This finding proved not merely scientifically interesting; it also changed clinical practice. Patients whose tumors harbored EGFR mutations experienced remarkable palliative improvement when they took oral drugs such as gefitinib or erlotinib, which block the kinase domain of the EGFR protein and are now approved for tumors that carry these mutations. However, not all EGFR mutations are predictive of response to EGFR inhibitors and in specific EGFR exon 20 insertions (the third most common type of EGFR mutations) constitute the majority of insensitive mutations.
Our group is focused in studying why EGFR exon 20 insertion mutations are different than other EGFR mutations and on how to develop novel treatment strategies for tumors that harbor these changes. To understand the patterns of resistance to EGFR inhibitors of EGFR exon 20 insertion mutations, in the first phase of the grant period, our research team generated the most extensive preclinical database of representative mutations using in vitro systems, structural models and NSCLC cell lines with these specific EGFR mutations. With the support of the LCFA grant, we now understand the basic structure of the most prevalent EGFR exon 20 insertion mutations and why drugs like gefitinib and erlotinib are unable to inhibit these mutations. The next phase of the research period will be focused on expanding our research tools and in using these to identify novel therapies that function as precision therapies for EGFR exon 20 insertion mutated lung cancers.
About the LCFA:
LCFA was established by two lung cancer survivors and a lung cancer widow. Although their life experiences vary greatly the three of them arrived at the same realization: the poor survival rate for lung cancer is a direct result of the lack of funding for lung cancer research. Working with many of the top lung cancer researchers and clinicians in America, LCFA has seen how lung cancer researchers are trying diligently to unlock the secrets unique to lung cancer. They have also witnessed the inordinate amount of time researchers spend in an effort to secure money to pay for the research, an effort that distracts them from their primary research function. The abysmal state of funding for lung cancer research also discourages new researchers who, instead, gravitate to where the money is, leaving a potential gaping hole in future lung cancer research programs.
The Lung Cancer Foundation of America’s mission is to save lives by dramatically increasing the five-year survival rates for all stages of lung cancer, the nation’s leading cause of cancer deaths for both men and women. LCFA will accomplish this by providing the necessary and critical funding for creative and leading edge lung cancer research programs for early detection, treatment options and hopefully, a cure. www.lcfamerica.org.