The past two decades have witnessed a fundamental reimagining of how we approach lung cancer diagnosis and treatment. What was once understood as a single disease requiring broad-based interventions has been transformed into a collection of distinct molecular subtypes, defined by tumor biomarkers, each with specific treatment opportunities.
By Anthony Sireci, M.D., senior vice president of clinical biomarkers, laboratories and diagnostics at Eli Lilly and Company
RET-fusion positive non-small cell lung cancer (NSCLC) represents approximately 1-2% of all NSCLC cases, yet for the thousands of people living with this specific molecular driver, targeted precision medicine can be transformative.1
Comprehensive genomic profiling (CGP) sits at the center of this progress. By identifying the specific genomic alterations that may be driving an individual’s cancer, CGP enables treatment selection based on biomarkers rather than stage of disease alone.
Decoding RET Fusions: What the Biology Reveals
RET fusions represent a distinct oncogenic mechanism—a chromosomal rearrangement where the RET gene breaks and fuses with another gene, creating an abnormal fusion protein that continuously drives cancer cell growth and division. Unlike RET point mutations in lung cancer, RET fusions are particularly potent drivers of cancer proliferation, making them an ideal target for precision-guided therapy.
Historically, people living with RET-fusion positive NSCLC faced a diagnostic challenge: their cancer’s true driver went undetected, leaving them to receive conventional chemotherapy or broad immunotherapy approaches that didn’t address their tumor’s underlying biology, with no treatment options that targeted RET-fusion positive cancer specifically prior to 2019. CGP enables systematic identification of RET fusions at diagnosis, a critical first step toward precision treatment.
Advances in Targeting RET
The timing of RET detection is critical to improving outcomes. When CGP is performed at diagnosis, patients and their care teams gain critical information that may inform every subsequent treatment decision. This is particularly important for those who are RET fusion-positive, as targeted therapies are being studied in earlier stages of treatment, potentially ensuring access to more options at multiple stages of cancer.
Empowering People Through Molecular Understanding
For people diagnosed with lung cancer, one of the most important conversations to have with a healthcare provider is about biomarker testing through CGP. Understanding whether your tumor harbors a RET fusion—or any other actionable molecular driver, like ALK, EGFR or KRAS G12C—fundamentally changes your treatment options and prognosis. Biomarker testing at diagnosis provides valuable information to guide personalized treatment selection and support informed early treatment decisions that can help preserve options and flexibility throughout the course of treatment.
For those who are RET-fusion positive, precision medicine options exist. It begins with a single, critical step: comprehensive genomic profiling at diagnosis. Equipped with this information, you and your care team can make treatment decisions that harness the full power of precision medicine—transforming outcomes through biology-driven, targeted therapy.
If you have been diagnosed with lung cancer, ask your healthcare provider about CGP. If results identify a RET fusion, understand that targeted therapies designed specifically for your cancer’s biology are available. This is precision medicine in practice: treatment guided by your cancer tumor’s unique molecular profile rather than by stage alone.
Guest Author Bio:
Anthony “Nino” Sireci, MD is the senior vice president of clinical biomarkers, laboratories and diagnostics at Eli Lilly and Company.
Dr. Sireci is a board-certified Clinical Pathologist and a practicing molecular pathologist. Prior to joining Lilly, he was an Assistant Professor of Pathology and Cell Biology at Columbia University and a medical director in the Laboratory of Personalized Genomic Medicine at Columbia Medical Center.
He is an active member of the Association for Molecular Pathology (AMP) where he serves on the organization’s Strategy Committee and was the former vice chair for new codes and pricing on the Economic Affairs Committee. He is also a member of the Pathology Coding Caucus in the College of American Pathologists (CAP) and the Molecular Pathology Advisory Group in the American Medical Association (AMA).
Dr. Sireci received a bachelor’s degree in chemistry from New York University, a medical degree from the Johns Hopkins University School of Medicine, and a master’s degree in Biostatistics from the Mailman School of Public Health at Columbia University. He completed his residency training in Clinical Pathology in the New York Presbyterian Hospital-Columbia, where he also served as chief resident.
References
Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2020;383(9):813-824. doi:10.1056/NEJMoa2005653
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