Understanding SCLC heterogeneity and plasticity in cancer metastasis and chemotherapy resistance

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases and features a strong predilection for early metastasis and extremely poor prognosis. Despite being highly sensitive to chemotherapy and/or radiotherapy initially, most SCLC patients develop therapeutic resistance within one year and die of distant metastases. Multiple studies have revealed the high heterogeneity and strong plasticity of SCLC associated with frequent metastases and early development of therapeutic resistance as well as poor clinical outcome. Importantly, different SCLC subtypes are associated with different therapeutic vulnerabilities, and the inflamed subtype tends to have the best response to immunotherapy, which highlights the importance of precision medicine in the clinic. Here, we review recent advances in SCLC heterogeneity and plasticity and their link to distant metastases and chemotherapy resistance. We hope that a better understanding of the molecular mechanisms underlying SCLC malignant progression will help to develop better intervention strategies for this deadly disease.