My name is Mohammed Al-Fazit, and on behalf of my team, I'll be presenting our poster entitled Small Cell Lung Carcinomas, Clinical Versatility as a Manifestation of its Shape-Shifting Cellular Programs. Despite some indications that small cell lung carcinomas may comprise distinct cell types, the extent of human small cell lung carcinomas intratumoral heterogeneity and the direct observation of subtype switching has been elusive to date. In this study, we show that treatment naive small cell lung carcinomas are substantially more heterogeneous than previously appreciated with most samples retaining two or more subpopulations. We established that most tumors contain cells that can access transcriptional states marked by a acute scoot, neuro D1 or yap one. We also show that the relative frequency of each state varied across tumors and that there could be substantial interconversion between states and individual tumors. We conclude that there are stable attractors in the gene network topology of most small cell lung carcinomas characterized by the expression of the state defining genes. Therefore we elucidate a spectrum of states of small cell lung carcinoma cells and their dynamics identify cellular programs that recapitulate neuroendocrine, neural and mesenchymal development. Our work overall advances a new unified model of cellular states and program diversity in this disease and nominates therapeutic strategies designed to limit its plasticity.

small cell lung carcinoma

SCLC

treatment naive

cellular programs

transcriptional states