Epigenetic landscape of small cell lung cancer: small image of a giant recalcitrant disease

Parvez Khan, Jawed Akhtar Siddiqui, Shailendra Kumar Maurya, Imayavaramban Lakshmanan, Maneesh Jain, Apar Kishor Ganti, Ravi Salgia, Surinder Kumar Batra, Mohd Wasim Nasser

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations


Small cell lung cancer (SCLC) is a particular subtype of lung cancer with high mortality. Recent advances in understanding SCLC genomics and breakthroughs of immunotherapy have substantially expanded existing knowledge and treatment modalities. However, challenges associated with SCLC remain enigmatic and elusive. Most of the conventional drug discovery approaches targeting altered signaling pathways in SCLC end up in the ‘grave-yard of drug discovery’, which mandates exploring novel approaches beyond inhibiting cell signaling pathways. Epigenetic modifications have long been documented as the key contributors to the tumorigenesis of almost all types of cancer, including SCLC. The last decade witnessed an exponential increase in our understanding of epigenetic modifications for SCLC. The present review highlights the central role of epigenetic regulations in acquiring neoplastic phenotype, metastasis, aggressiveness, resistance to chemotherapy, and immunotherapeutic approaches of SCLC. Different types of epigenetic modifications (DNA/histone methylation or acetylation) that can serve as predictive biomarkers for prognostication, treatment stratification, neuroendocrine lineage determination, and development of potential SCLC therapies are also discussed. We also review the utility of epigenetic targets/epidrugs in combination with first-line chemotherapy and immunotherapy that are currently under investigation in preclinical and clinical studies. Altogether, the information presents the inclusive landscape of SCLC epigenetics and epidrugs that will help to improve SCLC outcomes.

Original languageEnglish (US)
Pages (from-to)57-76
Number of pages20
JournalSeminars in Cancer Biology
StatePublished - Aug 2022


  • DNA methylation
  • Epigenetic modifications
  • Histone acetylation
  • Neuroendocrine carcinoma
  • Small cell lung cancer

ASJC Scopus subject areas

  • Cancer Research


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