2021 Targeted Therapies of Lung Cancer (TTLC) Meeting - Posters-P05. Detection of DNA Replication Blocker SLFN11 in Tumor Tissue and Circulating Tumor Cells to Predict Platinum Response in Small Cell Lung Cancer

P05. Detection of DNA Replication Blocker SLFN11 in Tumor Tissue and Circulating Tumor Cells to Predict Platinum Response in Small Cell Lung Cancer - PDF

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A study presented at the SCLC Virtual Platform discussed the potential of using the biomarker SLFN11 to predict platinum response in small cell lung cancer (SCLC). SCLC is known for its aggressiveness and high relapse rate, making the identification of predictive biomarkers crucial for treatment decisions. SLFN11 is a DNA/RNA helicase that blocks replication at stressed replication forks and has shown promise as a predictive biomarker for agents targeting DNA damage.<br /><br />The study aimed to characterize the prevalence, heterogeneity, and predictive value of SLFN11 in SCLC. The researchers developed and validated an immunohistochemistry (IHC) assay and a novel circulating tumor cell (CTC) assay to detect SLFN11 expression in tumor tissue and CTCs, respectively. They analyzed clinical tumor samples from three separate trial cohorts and found that approximately 50% of SCLC samples expressed SLFN11 by IHC. The expression levels varied, suggesting heterogeneity. CTC analyses confirmed that SLFN11 was expressed in about 50% of treatment-naïve patients but decreased significantly in patients receiving platinum treatment and at relapse.<br /><br />The researchers also observed morphological heterogeneity within and between patients, with SLFN11 expression independent of morphologic subtype. Interestingly, SLFN11 expression was found in white blood cells in blood samples and was highest in platinum-naïve patients and lowest in patients receiving platinum. This highlights the potential of SLFN11 as a predictive biomarker in SCLC.<br /><br />The findings have prompted the use of SLFN11 positivity by IHC for patient selection in an ongoing clinical trial. Additionally, blood-based CTC analyses are considered valuable for detecting SLFN11 expression, especially when tumor tissue is difficult to obtain. The dynamic nature of SLFN11 expression makes CTC analyses useful for longitudinal monitoring and potentially influencing treatment choices and response in real-time. Overall, this study emphasizes the potential of SLFN11 as a predictive biomarker and the importance of personalized approaches in SCLC treatment.

Keywords

SCLC

small cell lung cancer

biomarker

SLFN11

platinum response

predictive biomarkers

DNA damage

immunohistochemistry assay

circulating tumor cell assay

morphological heterogeneity