Small cell lung cancer transdifferentiation: not a negligible phenomenon

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.