LUNGevity Award Sparks New Biomarker Research for Patients with NSCLC

Juhi Kunde, Director of Patient Gateways and Science Marketing

When Sean Pitroda, MD, reached out to the Grants Office at the University of Chicago, he was looking for additional funding to continue his research into treating colorectal cancer with immunotherapy. Working with institutional grants from the university had yielded exciting findings, but he needed additional funding to continue his research.  

The person at the Grants Office suggested he apply for LUNGevity’s Career Development Award (CDA), a coveted award for junior faculty members that provides exceptional support and mentorship opportunities. “I hadn’t considered working on lung cancer before, but when I started looking into it, I saw the potential for crossover between my colorectal cancer research and the needs of the lung cancer community,” explained Dr. Pitroda, assistant professor of Radiation and Cellular Oncology at University of Chicago. “LUNGevity got me excited to work in lung cancer.”

Dr. Pitroda received the LUNGevity award in 2020 and, just two years later, his remarkable research findings were published last week in Nature Cancer and Nature Genetics — prestigious peer-reviewed academic journals. This work is likely to improve outcomes for patients with many types of cancer, including metastatic non-small cell lung cancer (NSCLC), by helping to personalize their treatment plans.

Sean Pitroda, MD

Nature Cancer

The findings published in Nature Cancer offer a roadmap to determine the optimal approach for combining radiation and immunotherapy for patients with metastatic NSCLC. It is well known that immune cell activity near the tumor increases the effectiveness of immunotherapy treatment. The current thinking in the field is that radiation therapy could activate the immune system and increase the effectiveness of subsequent immunotherapy. However, Dr. Pitroda’s work demonstrates that, in fact, radiation does not stimulate the immune system in all patients.

His work identifies an important new biomarker found in approximately 50% of patients with metastatic NSCLC and provides a strong rationale to treat a subset of these patients with a combination of radiation and immunotherapy for improved outcomes.

This research shows that approximately 50% of NSCLC tumors have a high degree of aneuploidy, or abnormalities in the number of chromosomes in the tumor cells. Tumors with high aneuploidy are less likely to have an activated immune response around the tumor, which reduces the effectiveness of immunotherapy. The research team also showed that radiation alone doesn’t effectively kill the high-aneuploidy tumor cells. “But the combination treatment worked effectively to kill those high-aneuploid tumor cells,” explained Dr. Pitroda. “For patients who would be treated with immunotherapy for their lung cancer and who also have a high-aneuploidy biomarker, our studies suggest they may benefit from adding radiation therapy to the treatment plan.”

Nature Genetics

The research published in Nature Genetics broadens the work from NSCLC to include many cancer types, such as colorectal cancer, breast cancer, brain tumors, and melanoma. The study shows high-aneuploidy is a biomarker that is found in all of these cancer types. Similar to what was seen in NSCLC, the tumor cells with high-aneuploidy have a reduced response to immunotherapy alone, regardless of the cancer type.

This information is helpful particularly when used with another common biomarker, tumor mutational burden (or TMB). TMB is the total number of DNA mutations found in cancer cells. For tumor cells with high TMB, immunotherapy is often an effective treatment. However, the majority of cancer patients (approximately 80%) have a low TMB where the effectiveness of immunotherapy is often unclear. Dr. Pitroda’s work helps to clarify the approach for patients with low TMB. His findings show that having a low degree of aneuploidy is likely to predict effective outcomes from immunotherapy for patients with low TMB. 

Future Projects and Collaborations

Dr. Pitroda and his team are continuing to expand the scope of this work as the findings reveal new insights into the development of lung cancer and other cancers. Many new and exciting projects are emerging from this work, such as building collaborations with commercial partners to create biomarker tests for aneuploidy, empowering other researchers to stratify patients based on aneuploidy, and conducting studies to understand the biology of aneuploidy better.

“It is key to understand why some cancer cells become highly aneuploid,” notes Dr. Pitroda. “We are already working to understand why tumor cells with high aneuploidy have a poor immune response. Once we understand these mechanisms, we can identify the vulnerabilities of these tumor cells and create personalized treatment approaches.”  

“I’m so grateful for the opportunity to venture into lung cancer research,” says Dr. Pitroda. “The support from LUNGevity, not just financially but also the mentorship, has been tremendous. The required presentations at LUNGevity science meetings gave me access to top lung cancer researchers for advice and discussions. Through these meetings, I’ve found strong research opportunities and collaborations that have helped my team conduct this impactful research.”

Dr. Pitroda plans to continue his progress by applying for a large federal grant in early 2023. “Having a Career Development Award from LUNGevity Foundation on your CV lends a lot of credibility to your work. It helps to gain grants from the NIH. I think it’s required to get to the next level of research; without it, I would be in a very different place right now.”

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