Dr Sen on the Goal to Identify Actionable Biomarkers of Interest in SCLC

Triparna Sen, PhD, cell and molecular biologist, associate professor, Department of Oncological Sciences, director, Lung Cancer PDX Platform, Icahn School of Medicine at Mount Sinai, discusses the importance of identifying actionable or targetable biomarkers for the treatment of patients with small cell lung cancer (SCLC).

Identifying effective biomarkers for SCLC is challenging, Sen begins, as SCLC doesn’t lend itself to mutation-driven biomarkers due to its high mutation rate, often resulting from patients’ long histories of smoking. This makes mutation-based biomarkers ineffective when making clinical decisions in SCLC, she explains. Consequently, research focuses in SCLC have shifted to expression-based biomarkers, which are more dynamic and complex to implement, Sen reports.

At present, there are no established biomarkers for selecting SCLC treatments; however, developments are emerging in both preclinical and clinical research, she continues. One key area of exploration involves identifying distinct subtypes of SCLC, according to Sen. These subtypes are characterized by transcriptomic and proteomic profiles, and can be broadly divided into 4 categories, including major neuroendocrine subtypes, non-neuroendocrine subtypes, and prominent immune gene signatures, Sen states. However, these subtypes require validation through prospective clinical trials to determine their relevance as biomarkers, she elucidates.

There is a potential need to reclassify these SCLC subtypes because they might represent different cell states rather than distinct categories, she says. Sen also highlights the biomarker Schlafen 11 (SLFN11), which was initially evaluated in preclinical studies and retrospectively validated in a trial involving veliparib (ABT-888) and temozolomide (Temodar). SLFN11 was later prospectively evaluated in the phase 2 SWOG S1929 trial (NCT04334941). This trial selected patients with SCLC based on SLFN11 expression levels and tested the efficacy of combining a PARP inhibitor with immunotherapy, she explains. The results indicated that patients with high SLFN11 expression hadmarginally better progression-free survival outcomes than those with low SLFN11 expression, Sen adds.

Although these findings demonstrate the potential for biomarker-driven treatment approaches in SCLC, they also underscore that more research is needed, she expands. The field is still evolving, and there is a significant amount of work required to refine and validate these biomarkers before they can be reliably used in clinical settings, Sen concludes.