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Updated: May 7, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Targets in small cell lung cancer
1National Cancer Institute, Bethesda, MD, United States.
Abstract:
Recurrent small cell lung cancer is a recalcitrant malgnancy. The application of genomic technologies has begun to elucidate the large number of genetic abnormalities in SCLC. Several cell surface receptors are known to be overexpressed by SCLC in clinic specimens and cell in culture including GPCRs such as the bradykinin receptor, the chemokine receptor CXCR4, the vasopression receeptor and the three bomebsin receptors. The glucose transporter GLUT1, the tetraspanin family member PETA/CD151 and the immunoglobulin superfamily member ALCAM/CD166 are also overexpressed by SCLC. NCAM/CD56 is overexpressed by nearly all SCLC and is currently the target for an antibody drug conjugate in Phase II trial. Although SCLC is not considered a RTK driven disease, IGF1R and FGFRs are often overexpressed by SCLC. SCLC abberantly expresses several developmental transcription factors including ASCL1, SOX2, 4, and 11, OCT4, NANOG, PAX5; however, overexpression of MYC may be a driver in SCLC. Like other cancers, SCLC expresses survival factors and uses aerobic glycolysis as a major source of ATP. The drawback of many potential targets overexpressed by SCLC is expression of the same proteins by normal tissues. We are slowly learning more about the molecular abnormalities that occur in SCLC; however, therapeutic impact from new findings remains a goal to work toward.
Insights
Recurrent small cell lung cancer (SCLC) is challenging, but genomic studies reveal numerous genetic abnormalities. Identifying overexpressed targets like NCAM/CD56 offers potential therapeutic avenues despite challenges with normal tissue expression.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Recurrent small cell lung cancer (SCLC) presents significant therapeutic challenges.
- Genomic technologies are increasingly used to understand the molecular landscape of SCLC.
- Several cell surface receptors and developmental transcription factors are aberrantly expressed in SCLC.
Purpose of the Study:
- To elucidate the genetic abnormalities in recurrent small cell lung cancer.
- To identify potential therapeutic targets overexpressed in SCLC.
- To review the current understanding of molecular alterations in SCLC.
Main Methods:
- Genomic profiling of SCLC specimens.
- Analysis of cell surface receptor and transcription factor expression.
- Review of existing literature on SCLC molecular abnormalities.
Main Results:
- Overexpression of GPCRs (bradykinin, chemokine CXCR4, vasopressin, bombesin receptors), GLUT1, PETA/CD151, ALCAM/CD166, and NCAM/CD56 in SCLC.
- IGF1R and FGFRs are frequently overexpressed, though SCLC is not typically considered RTK-driven.
- Aberrant expression of developmental transcription factors (ASCL1, SOX2, OCT4, NANOG) and potential MYC-driven alterations identified.
Conclusions:
- NCAM/CD56 is overexpressed in most SCLC cases and is a target for antibody drug conjugates.
- A significant challenge for targeted therapy is the expression of potential targets in normal tissues.
- Continued research into SCLC molecular abnormalities is crucial for developing effective therapeutics.
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