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Small cell lung cancer transdifferentiation : not a negligible phenomenon

Horvath, Lilla ; Boettiger, Kristiina ; Megyesfalvi, Zsolt ; Döme, Balázs LU ; Aigner, Clemens ; Horváth-Rózsás, Anita and Berta, Judit (2025) In Current Opinion in Oncology 38(1). p.39-46
Abstract

Purpose of review – Small cell lung cancer (SCLC), particularly its transdifferentiated form, is highly aggressive and has a poor prognosis. The diagnosis of SCLC transdifferentiation is challenging, as repeat biopsies are often not clinically feasible and few noninvasive predictors of this neuroendocrine transformation have been identified to date. Recent findings – Some retrospective studies and case reports have investigated this phenomenon. These studies indicate that it can occur in nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, or rearranged during transfection (RET) fusions, typically following treatment with tyrosine kinase... (More)

Purpose of review – Small cell lung cancer (SCLC), particularly its transdifferentiated form, is highly aggressive and has a poor prognosis. The diagnosis of SCLC transdifferentiation is challenging, as repeat biopsies are often not clinically feasible and few noninvasive predictors of this neuroendocrine transformation have been identified to date. Recent findings – Some retrospective studies and case reports have investigated this phenomenon. These studies indicate that it can occur in nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, or rearranged during transfection (RET) fusions, typically following treatment with tyrosine kinase inhibitors. However, it has also been observed in cases of EGFR-wild type NSCLC after immunotherapy or radiation therapy. Summary – Several molecular mechanisms that can drive SCLC transdifferentiation have been identified. The treatment of transdifferentiated SCLC remains a significant challenge, although promising new strategies are currently under investigation. This review summarizes the current understanding of SCLC transdifferentiation.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
molecular drivers, small cell lung cancer, therapeutic approaches, transdifferentiation
in
Current Opinion in Oncology
volume
38
issue
1
pages
39 - 46
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:41263473
  • scopus:105027797731
ISSN
1040-8746
DOI
10.1097/CCO.0000000000001205
language
English
LU publication?
yes
id
427ced84-3486-4871-a76a-a6b2cd2c5b08
date added to LUP
2026-02-27 10:19:17
date last changed
2026-09-28 07:27:03
@article{427ced84-3486-4871-a76a-a6b2cd2c5b08,
  abstract     = {{<p>Purpose of review – Small cell lung cancer (SCLC), particularly its transdifferentiated form, is highly aggressive and has a poor prognosis. The diagnosis of SCLC transdifferentiation is challenging, as repeat biopsies are often not clinically feasible and few noninvasive predictors of this neuroendocrine transformation have been identified to date. Recent findings – Some retrospective studies and case reports have investigated this phenomenon. These studies indicate that it can occur in nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, or rearranged during transfection (RET) fusions, typically following treatment with tyrosine kinase inhibitors. However, it has also been observed in cases of EGFR-wild type NSCLC after immunotherapy or radiation therapy. Summary – Several molecular mechanisms that can drive SCLC transdifferentiation have been identified. The treatment of transdifferentiated SCLC remains a significant challenge, although promising new strategies are currently under investigation. This review summarizes the current understanding of SCLC transdifferentiation.</p>}},
  author       = {{Horvath, Lilla and Boettiger, Kristiina and Megyesfalvi, Zsolt and Döme, Balázs and Aigner, Clemens and Horváth-Rózsás, Anita and Berta, Judit}},
  issn         = {{1040-8746}},
  keywords     = {{molecular drivers; small cell lung cancer; therapeutic approaches; transdifferentiation}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{39--46}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Current Opinion in Oncology}},
  title        = {{Small cell lung cancer transdifferentiation : not a negligible phenomenon}},
  url          = {{http://dx.doi.org/10.1097/CCO.0000000000001205}},
  doi          = {{10.1097/CCO.0000000000001205}},
  volume       = {{38}},
  year         = {{2025}},
}