Exploring copy number alterations (CNAs) to gain new insight into SCLC heterogeneity

Small-cell lung cancer (SCLC) is a highly aggressive tumor with high proliferation and metastatic potential. Due to its nature, it constantly remains one of the leading causes of cancer-related deaths around the world. Moreover, therapeutic options for SCLC patients are still limited. Even though our knowledge of SCLC has increased in recent years, it remains insufficient to identify reliable biomarkers and precisely guide therapy. High intra- and inter-patient heterogeneity appears to be one of the leading issues. Moreover, SCLC has the ability to reprogram during the course of the disease and under the pressure of treatment. This may result in the development of resistance to initially effective therapy. Although identification of molecular subtypes was a major breakthrough in studies on SCLC, defining the subtype alone seems to be insufficient to personalize patients' management. Therefore, there is ongoing research to identify additional biomarkers. Copy number alterations (CNAs) are known to affect genes expression in various oncological cohorts, and SCLC is reported to exhibit a high CNA burden. Analysis of numerical alterations may be one of the keys to uncovering its drivers and diversity. In this review, we discuss nomenclature and methodological issues concerning CNAs assessment. Subsequently, we summarize current knowledge regarding the most frequent CNAs in the SCLC cohort, as well as the latest studies that point directions worth further investigation. We put emphasis both on tumor tissue- and liquid biopsy-derived CNAs as each of these approaches seems to be highly valuable for uncovering SCLC heterogeneity.