Targeting the RAS-dependent chemoresistance: The Warburg connection

Publication date: Available online 9 February 2018 Source:Seminars in Cancer Biology Author(s): Roberto Serna-Blasco, Marta Sanz-Álvarez, Óscar Aguilera, Jesús García-Foncillas RAS protein family members (KRAS4A, KRAS4B, HRAS and NRAS) function as GDP–GTP-regulated on-off switches, which regulate cytoplasmic-nuclear signaling networks ruling diverse normal cellular processes. Constitutive activating mutations in RAS genes are found in up to 30% of human cancers, and remarkably, the oncogenic Ras mutations and mutations in other components of Ras/MAPK signaling pathways seem to be mutually exclusive in most tumors, pointing out that deregulation of Ras-dependent signaling is an essential requirement for tumorigenesis. Up to 30% of solid tumors are known to have a mutated (abnormal) KRAS gene. Unfortunately, patients harboring mutated KRAS CRC are unlikely to benefit from anti-EGFR therapy. Moreover, it remains unclear that patients with KRAS wild-type CRC will definitely respond to such therapies. Although some clinically designed-strategies to modulate KRAS aberrant activation have been designed, all attempts to target KRAS have failed in the clinical assays and K-RAS has been assumed to be invulnerable to chemotherapeutic attack. Recently, different encouraging publications reported that ascorbate may have a selective antitumoral effect on KRAS mutant cancer cells. In this review we aim to describe the prevalence and importance of KRAS mutation in cancer and asso...

Source: Seminars in Cancer Biology - March 17, 2018 Category: Cancer & Oncology Source Type: research