This study, published in the journal JTO Clinical and Research Reports, examined more than 60 tumors from five patients. OSUCCC – James researchers identified distinct mutational and molecular changes in four SCLC subtypes. The findings provide new insights into the patterns' treatment resistance and could offer new targets for the development of more effective immunotherapy and other therapies for advanced SCLC, which progresses quickly and is usually fatal.
SCLC accounts for up to 15% of lung cancer cases worldwide. The disease often responds well to chemotherapy when first diagnosed but then recurs in a lethal, treatment-resistant form.
“Advanced SCLC often does not respond as well to immune therapies that are effective in other types of lung cancer, and the reasons for this are poorly understood,” says principal investigator Sameek Roychowdhury, MD, PhD, a medical oncologist and member of the OSUCCC – James Translational Therapeutics Program. He is also an associate professor in the Ohio State College of Medicine’s Division of Medical Oncology and medical director of the OSUCCC – James Clinical Laboratory Improvement Amendments (CLIA) Cancer Genomics Laboratory. Other authors of the study include Hui-Zi Chen, MD, PhD; Russell Bonneville, PhD; and Anoosha Paruchuri, PhD, all of whom received Pelotonia Fellowships. “Our findings suggest that the causes of treatment resistances in advanced SCLC may be subtype-specific,” says Roychowdhury. “They also highlight the importance of tumor genomic studies to identify the most effective therapies for these patients and to support development of new therapies for this often-fatal disease.”
Genomics is the process of identifying cancer-related mutations that drive the growth and spread of cancers. Oncologists can gather genomic information from individual patients to help match them with the best therapy based on their unique tumor characteristics. This concept is referred to as precision cancer medicine. This approach has important significance in metastatic and rare forms of cancer, where treatment options are often limited.
“Understanding the specific drivers of a person’s cancer can help us identify potential alternative treatment options through clinical trials that would not have been possible otherwise,” adds Roychowdhury.
For this study, Roychowdhury and his colleagues analyzed genomic DNA and total mRNA from tumor cells removed from five deceased patients with advanced SCLC, along with circulating tumor DNA. The tissue was obtained as part of a rapid research autopsy study, originally supported by a Pelotonia Idea Grant. Tissue was collected within 16 hours of each patient’s passing, minimizing the molecular changes that occur in cells after death.
The five patients had consented to undergo a research autopsy soon after death to allow the researchers to collect and evaluate many tumors. The researchers used sequencing technologies to identify genetic and molecular changes in four SCLC tumor subtypes. Many of the changes are associated with resistance to immune therapy and other treatments.