Joseph Minhow Chan, MD, PhD

Large cell neuroendocrine carcinoma (LCNEC) is an aggressive lung cancer type with few treatment options, due to poor understanding of the disease. LCNEC shares molecular features of two other lung cancers—lung adenocarcinoma and small cell lung cancer. It can coexist with them in the same tumor, making diagnosis challenging. Previous studies have focused on analyzing the entire tumor, missing the variability within and interactions with the immune environment (the ecosystem that surrounds the tumor, including immune cells, blood vessels and other cells). This variability, known as intratumoral heterogeneity (ITH), can hide potential drug targets and resistant cell types. We will study this variability in the tumor and its environment. We will map the genomic diversity within LCNEC tumors, develop an AI-based LCNEC classifier using genetic and structural data, and investigate the results of interactions between tumors and the immune system in LCNEC. These findings aim to enhance diagnosis of this type of lung cancer and uncover new therapies, including targeted treatments and immunotherapies.

Update: Over the past year, we have made significant progress in understanding high-grade neuroendocrine lung cancer by completing the largest single-nucleus RNA sequencing dataset of large cell neuroendocrine carcinoma (LCNEC) to date. Through this work, we identified multiple molecular subtypes and potential vulnerabilities. Our work aims to guide new treatment strategies for patients with high-grade neuroendocrine lung cancer, for whom few targeted or immunotherapies currently exist.