Two Indiana University School of Medicine hematology-oncology fellows are digging deep into timely cancer research questions, with research support provided by the George and Sarah Jane Fisher Fund.

Melissa Yan, MD, and Nikhil Shukla, MD, are investigating biomarkers that may one day provide more personalized solutions in treating lung cancer. Each award recipient received $6,000 to support their oncology research. William B. Fisher, MD, co-founder of Hoosier Cancer Research Network (HCRN) established the George and Sarah Jane Fisher Fund in the late 1990s in memory of his mother, Sarah Jane, and brother, George, both of whom died of cancer.

Dr. Yan, who received her medical degree from St. George’s University School of Medicine in West Indies, Grenada, is using her award to support research in adults with unresectable stage III non-small cell lung cancer (NSCLC). She is looking into the incidence of serine/threonine kinase 11 (STK11) and Kelch-like ECH-associated protein 1 (KEAP1) mutations.

“There have been some molecular determinants such as STK-11 mutation and KEAP1 mutation that have emerged as potential biomarkers for resistance to immunotherapy with PD-1 or PD-L1 inhibitors,” Dr. Yan explained. “The goal of the project is to estimate the incidence of these specific mutations and to determine if there is a predictive value in these mutations to consolidation immunotherapy in patients with stage III non-small cell lung cancer who were treated on the Big Ten Cancer Research Consortium’s BTCRC-LUN16-081 trial.”

This randomized phase II study tests consolidation therapy with nivolumab and ipilimumab or nivolumab alone following concurrent chemoradiation in adults with unresectable stage IIIA or IIIB NSCLC.

“This funding allows me to obtain genome sequencing for these patients to look for these specific mutations and to follow their outcomes with consolidation immunotherapy,” Dr. Yan said.  “If these mutations are validated as negative predictive biomarkers, the presence of STK11 and/or Keap1 mutations has the potential to spare patients the unnecessary risks and financial burden of consolidation immunotherapy in this clinical setting.”

Dr. Yan’s research interests include the utilization of circulating tumor DNA and genetic biomarkers to help personalize therapy for patients with NSCLC. She has been working with her mentor, Nasser H. Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at the IU School of Medicine, a researcher at the IU Simon Comprehensive Cancer Center, and former chair of the HCRN Board of Directors.

“I want to thank Dr. Fisher for supporting this award for the fellows,” Dr. Yan said. “It means a lot to get this recognition and it gives us extra motivation to support our research. I feel very honored.”

She will complete her fellowship in 2021 and plans to pursue her medical career as a clinician, treating lung cancer.

Dr. Shukla, a graduate of the University of Louisville School of Medicine, is using his award for a pilot study that is looking at immunologic markers in metastatic non-small lung cancer. His study is trying to identify the amounts of different immune cells that are circulating in the patient to determine if a particular immunologic profile can predict response more accurately than just looking at a single biomarker. By looking at the ratios of regulatory B and T cells, myeloid suppressor cells, cytoxic T cells and helper T cells in patients, he’d like to better identify which patients respond favorably, which have stable disease, and which progress with immunotherapy.

Ten patients with metastatic NSCLC who are part of the pilot study are each receiving single agent immunotherapy – PD-1 or PD-L1 checkpoint inhibitors – in the first- or second-line setting.

“Once we establish with this pilot study that there may be a way to use the immunologic profile for a patient to actually predict response, then the next trial could be designed to determine if patients with certain immunologic profiles respond more favorably to checkpoint inhibitor therapy,” Dr. Shukla said.

He is currently working on the correlative portion of the Big Ten CRC Research Consortium study, BTCRC-LUN16-081, the same study to which Dr. Yan is contributing. Dr. Shukla’s focus, however, is on circulating tumor DNA (ctDNA). This type of DNA originates from cancerous cells and tumors and offers a non-invasive way to monitor disease progression through liquid biopsies.

“We’ve hypothesized that patients who clear their circulating tumor DNA while being treated have better outcomes and we may be able to shorten their therapy, thereby reducing potential adverse events that they may have from systemic therapy,” he said. “Once we determine patients who do clear circulating tumor DNA have better outcomes, then we can focus on the patients who don’t. The next steps would be to write new clinical trials to test hypotheses about novel therapeutics in patients with persistently detectable ctDNA despite receiving standard of care therapy. .”

In addition to serving as a fellow, Dr. Shukla is the IU/Lilly Developmental Therapeutics Fellow. He is working part time with Eli Lilly and Company this year and he will serve as a clinical research physician at Lilly next year, working on early phase oncology research.

Dr. Shukla expressed his gratitude for the Fisher family’s support.

“I’m very grateful to the Fisher family for this award,” he said. “I appreciate that they are philanthropically engaged and are trying to encourage young investigators in the clinical sciences, particularly oncology.”

During his fellowship, Dr. Shukla credits many mentors in guiding him in oncology research.

“At Indiana University there’s a very strong thoracic oncology program,” he said. “My mentor in the fellowship has been Dr. Nasser Hanna. I’ve also been mentored by other faculty in the thoracic program, namely Dr. Shadia Jalal, Dr. Greg Durm, and of course Dr. Lawrence Einhorn. I hope to pay it forward, that the work that I do can hopefully impact as many people as possible.”

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.