Surfaceome profiling revealed unique therapeutic vulnerabilities in transcriptional subtypes of small cell lung cancer (SCLC).


Taofeek K. Owonikoko, Andrew Elliott, Bhakti Dwivedi, Andrey Ivanov, Gabriel Sica, Sonam Puri, Abdul Rafeh Naqash, Kathleen Claire Kerrigan, Shiven B. Patel, Andreas Seeber, Florian Kocher, Dipesh Uprety, Hirva Mamdani, Amit Kulkarni, Gilberto Lopes, Balazs Halmos, Wallace L. Akerley, Stephen V Liu, Wolfgang Michael Korn, Hossein Borghaei

Key Findings: 

  • Small-cell lung cancer (SCLC) subtypes based on transcription factor expression patterns of ASCL1, NEUROD1, YAP1 and POU2F3, and the resultant four subtypes SCLC-A, SCLC-N, SCLC-Y and SCLC-P, have set the stage for development of more effective treatment strategies for this aggressive disease. 
  • We examined the surfaceome profiles of the SCLC subtypes using whole transcriptome sequencing of 674 small-cell lung cancer samples. 
  • The SCLC-Y subtype showed the highest expression of the gene that encodes the highly pursued drug target TROP2, TACSTD1, and its interacting and regulatory genes, suggesting this subtype could be a candidate for antibody-drug-conjugates targeting TROP2. 
  • Several additional candidate cancer/testis antigens and surfaceome genes showing strong correlation with lineage-defining transcription factors offer additional therapeutic targets in SCLC. 
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