Personalized medicine, in which the molecular profile of each patient’s tumor helps customize the course of treatment, has been useful in treating many types of cancer, including non-small cell lung cancer (NSCLC). However, for patients diagnosed with extensive small cell lung cancer (SCLC), the treatment plans are mostly one size fits all.
“The lack of treatment options for patients with extensive SCLC is due to many contributing factors,” notes Carl Gay, MD, PhD, assistant professor in the department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center. “One big issue facing scientists is a lack of SCLC tissue to use for research. Because SCLC is often diagnosed using only a small biopsy sample from a fine needle aspiration, we don’t have large collections of SCLC tissue samples.”
“Researchers need tissues samples from many patients so we can learn more about SCLC and then develop more effective treatments,” says Dr. Gay. “While researchers have identified three subtypes of SCLC based on activation of the ASCL1 (SCLC-A), NEUROD1 (SCLC-N), and POU2F3 (SCLC-P) genes, none of these three subtypes is particularly sensitive to immunotherapy, but in the clinical trials there is a subset of SCLC patients who are sensitive.”
Building upon his years of conducting research and treating cancer patients, Dr. Gay and his team set out to identify the subset of SCLC patients who can be successfully treated with immunotherapy.
“We took a completely unbiased approach. We knew there were SCLC tumors that didn’t fit into any of the three known subtypes, but we didn’t know how many more subtypes there would be,” explains Dr. Gay.
Using a computational approach, Dr. Gay and his collaborators input all the relevant gene expression data to determine how many subtypes were likely to be found.
“The answer was four. Fortunately, three of those subtypes were very similar to the three that were already known. This left us with the fourth subtype, the inflamed subtype (SCLC-I),” says Dr. Gay. “It was almost blindingly obvious that this subtype was likely to be the one that was sensitive to immunotherapy because it had T-cells infiltrating the tumor and expressed immune checkpoints -- characteristics of a tumor that can be successfully treated with immunotherapy.”
But Dr. Gay’s research team needed support to confirm this hypothesis in a clinical trial.
In 2020, Dr. Gay was awarded a Career Development Award (CDA) from LUNGevity Foundation to conduct a phase II clinical trial that tests the safety and efficacy of a promising drug combination (an immunotherapy to encourage immune activity combined with a PARP1 inhibitor to impede DNA repair).
Patients enrolled in the trial will provide robust biopsy samples before and after the treatment, so the researchers can study the effects of the treatment and conduct a retrospective analysis to determine which of the four known SCLC subtypes was the most sensitive to this treatment.
Dr. Gay and his team will also be using modern mouse model techniques to complement the clinical trial and deepen our understanding of PARP1 in tumor cells.
In his first year as a junior faculty member at MD Anderson, Dr. Gay needed LUNGevity’s support to make his research goals a reality. “I am so grateful for the CDA from LUNGevity. Those first years are so critical,” Dr. Gay says. “You need that research funding to justify your research abilities and ideas. You need to prove someone is willing to take a chance on you.”
This early CDA support often can be leveraged into larger research grants from governments or other organizations. In Dr. Gay’s case, CPRIT (the Cancer Prevention and Research Institute of Texas) awarded him a $1.5 million grant, based on his scientific track record and the CDA from LUNGevity. This funding will be used to build a comprehensive tissue collection and testing program for SCLC at MD Anderson to be used by clinical trials.
“My hope is that this will help to lay the foundation for personalized medicine in patients with SCLC,” says Dr. Gay. “That’s my ultimate goal – to run that clinical trial, the one that makes a real difference in people’s lives.”
“The lung cancer community has made great strides in helping patients diagnosed with NSCLC. And now we are finally starting to get a handle on SCLC,” says Dr. Gay. “With so many innovative tools and technologies at our disposal, the future is looking bright and full of hope.”