Researchers Identify mRNA Biomarker to Predict Response to Chemotherapy

A recent study sought to identify an mRNA biomarker that predicts chemosensitivity across multiple solid tumor subtypes, given the significant heterogeneity in response among patients to chemotherapies.

Molecular features of a tumor are being used to guide individual treatment decisions, and targeted therapies have been developed over the past 2 decades that are selective for overexpressed or mutant oncoproteins in cancer cells. But the researchers noted that approaches to leverage molecular features of tumors to customize conventional chemotherapies remain underdeveloped.

They hypothesized that molecular features of cancer cell line models could be used to identify a molecular predictor of response to chemotherapy in human tumors, based on the idea that cancer cell sensitivity to a chemotherapeutic may be associated with cancer cell—intrinsic molecular features.

The research involved correlation analyses involving 1190 cell lines and 56 drugs along into 5 different chemotherapeutic classes.

They identified Schlafen Family Member 11 (SLFN11) mRNA level as a biomarker predictive of response to chemotherapeutics, including topoisomerase inhibitors, alkylating agents, antimetabolites, and antitumor antibiotics in solid tumor lineages.

Additionally, SLFN11 mRNA level is a tumor biomarker predictive of overall survival and enhanced tumor response in patients with breast, lung, and ovarian cancer treated with these chemotherapeutics, the authors reported.

Further research will involve prospective clinical trials in multiple cancer subtypes to determine whether SLFN11 expression predicts tumor response, recurrence, progression, and survival in patients treated with topoisomerase inhibitors, alkylating agents, antimetabolites, or antitumor antibiotics; the work could lead to prescreening patients prior to chemotherapy to adjust treatment on an individual basis.

Reference

Shee K, Wells JD, Jiang A, Miller TW. Integrated pan-cancer gene expression and drug sensitivity analysis reveals SLFN11 mRNA as a solid tumor biomarker predictive of sensitivity to DNA-damaging chemotherapy [published online November 4, 2019]. PLoS One. doi: 10.1371/journal.pone.0224267.