Drug combinations identified by high-throughput screening promote cell cycle transition and upregulate Smad pathways in myeloma.

ABSTRACT: Drug resistance and disease progression are common in multiple myeloma (MM) patients, underscoring the need for new therapeutic combinations. A high-throughput drug screen in 47 MM cell lines and in silico Huber robust regression analysis of drug responses revealed 43 potentially synergistic combinations. We hypothesized that effective combinations would reduce MYC expression and enhance p16 activity. Six combinations cooperatively reduced MYC protein, frequently over-expressed in MM and also cooperatively increased p16 expression, frequently downregulated in MM. Synergistic reductions in viability were observed with top combinations in proteasome inhibitor-resistant and sensitive MM cell lines, while sparing fibroblasts. Three combinations significantly prolonged survival in a transplanta

SUBMITTER: Peat TJ 

PROVIDER: S-EPMC10408729 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature