Targeting SMARCAL1 as a novel strategy for cancer therapy

SMARCAL1 is a SNF2 chromatin-remodeling protein with ATP-dependent annealing helicase activity. Recent studies have shown that SMARCAL1 is involved in DNA damage repair and cell cycle progression. Deficiency of SMARCAL1 enhances the anticancer activity of chemotherapy agents and reverses cancer cell resistance to these agents. Therefore, targeting SMARCAL1 is an attractive therapeutic approach for cancers with defects in DNA damage repair or cell cycle checkpoints. Here, we review advances in our understanding of the biochemical and cellular functions of SMARCAL1 made over the recent years and discuss the rationale for development of SMARCAL1 inhibitors as novel anticancer therapies.

► Cancer cells have intrinsic deficiencies in DNA damage repair.
► Targeting DNA damage repair results in cancer cell death.
► Targeting DNA damage repair therapy is an example of synthetic lethality.
► We review the functions of SMARCAL1 in DNA damage repair and cell cycle progression.
► We discuss the rationale for targeting SMARCAL1 as a strategy for cancer therapy.