Team led by John Heymach, MD, PhD, secures $1.5 million grant

The Lung Cancer Research Foundation (LCRF) has announced the first recipients of its LCRF | Boehringer Ingelheim Team Science Award on Innovative Therapeutic Strategies to Understand and Treat Lung Cancers Harboring HER2 Mutations. This initiative, "Integrated molecular, structural and clinical studies to characterize and develop therapeutic approaches for tyrosine kinase inhibitor resistance and drug tolerant persister cells (DTPCs) in HER2 mutant non-small cell lung cancer (NSCLC)", stems from a key research partnership with Boehringer Ingelheim.

Leading the effort is John Heymach, MD, PhD, Professor of Thoracic/Head and Neck Medical Oncology and Chief of the Section of Thoracic Medical Oncology at the University of Texas MD Anderson Cancer Center. His collaborators include Samir M. Hanash, MD, PhD, Professor in the Department of Clinical Cancer Prevention-Research and Department of Molecular Pathology at MD Anderson; Michael Eck, MD, PhD, Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School; John W. Lawson, PhD, Computational Materials Group Leader at NASA Ames Research Center; and Heidi Greulich, PhD, Senior Group Leader and Institute Scientist at the Broad Institute of MIT and Harvard.

Lung cancer remains the top cause of cancer deaths globally. Among non-small cell lung cancer (NSCLC) cases, a portion features tumors fueled by HER2 gene mutations. Although newly approved HER2-targeted tyrosine kinase inhibitors (TKIs) mark significant advances, most patients face relapse as tumors build resistance to therapy. This team's work aims to uncover the roots of resistance and craft fresh tactics to surmount it, ultimately providing longer-lasting treatments for those with HER2-mutant lung cancer.

HER2-mutated lung cancers stand out as one of the toughest oncogene-driven NSCLC subtypes to manage. Even with recent nods for HER2-specific TKIs and antibody-drug conjugates (ADCs), benefits tend to fade quickly. Resistance in these patients arises mainly from two issues: alterations in the HER2 protein that block drug binding, and the emergence of alternative survival pathways bypassing HER2 entirely. Addressing both demands a multidisciplinary alliance spanning drug design, cell biology, computational modeling, and immunology.

The assembled experts unite diverse skills to tackle these hurdles through two focused projects, leveraging cutting-edge tools like AI. The initial effort employs deep mutational scanning, structural biology, and computational modeling to map resistance mutations in HER2 and predict TKI responses for both primary and resistant variants. The follow-up project maps HER2-independent resistance mechanisms to TKIs, while pioneering cellular therapies and T-cell engagers targeting drug-tolerant persister cells (DTPCs) and drug-resistant cells (DRCs). Promising targets will be validated, with successful therapies potentially advancing to a phase 1 clinical trial.

"Through analysis of tumor models and patient samples - from pre-treatment to minimal residual disease and full resistance - we will pinpoint shifts in gene expression, cell identity, and surface proteins," explains Dr. Heymach. "These insights will fuel lab and animal testing; strong results could propel a physician-initiated clinical trial, bringing new hope to patients with HER2-mutant tumors."

"This embodies peak synergy between lab and computational sciences," noted Antoinette Wozniak, MD, FASCO, Chief Scientific Officer at LCRF. "It promises faster breakthroughs, led by top talents in their domains."

"We are thrilled to back collaborative research advancing novel solutions for tough-to-treat cancers and unmet needs," stated Emmanuelle Clerisme-Beaty, Medical Director US, SVP Medicine at Boehringer Ingelheim. "Such teamwork speeds cancer progress, and we applaud these grant winners for their vital contributions to better patient futures."

About the Lung Cancer Research Foundation (LCRF)

The Lung Cancer Research Foundation® (LCRF) leads as the premier nonprofit driving innovative, high-impact research to prolong survival and enhance life for lung cancer patients. Its mission targets improved outcomes via funding for prevention, diagnosis, treatment, and cures. So far, LCRF has supported 450 grants worth nearly $53 million - the largest sum from any nonprofit in lung cancer research. Learn more about its grant programs at lcrf.org/research.

About Boehringer Ingelheim in Oncology
We aspire to transform cancer lives with breakthrough advances, aiming ultimately to cure diverse cancers. Boehringer Ingelheim's long-term innovation push shines in its pipeline of cancer cell-targeted and immuno-oncology therapies, plus smart combinations. In oncology, we pursue a thorough, broad strategy, forging collaborative networks to harness varied expertise - essential for tackling high-challenge, high-reward cancer areas. For us, cancer care is deeply personal, now and for generations.

Contact:
LUNG CANCER RESEARCH FOUNDATION (LCRF)
Sheila Sullivan, Sr. Director, Marketing & Communications, [email protected]

SOURCE Lung Cancer Research Foundation