SHP2 inhibitors: Recent advancements and potential breakthroughs in cancer therapy

Abstract

SHP2 (Src homology-2 domain-containing protein tyrosinephosphatase-2) works as a tyrosine phosphatase, to eliminate tyrosine phosphorylation in the non-receptor protein to link many oncogenic signaling pathways including RAS/RAF/MAPK and PI3K/AKT. Mutations and overexpression in SHP2 cause cancer and related abnormalities in the body including leukemia or solid tumors. Hence, SHP2 has piqued the interest of researchers as a target for inhibition. Several therapeutic compounds are undergoing clinical trials where SHP2 undergoes conformational modifications by binding either inside or outside the catalytic pocket of PTP. These compounds impact different types of cancer with varying efficiencies indicating their excellent chemotherapeutic potential. Therefore, this review has explored the function and structure of SHP2, its relationship with cancer, and strategies to target its catalytic pocket and allosteric regions as an effective cancer treatment option. Additionally, an insight into these compounds’ prospects has portrayed their advancements and limitations in cancer treatment through modulation of SHP2.