The three RAS genes, including KRAS, NRAS, and HRAS, are among the most frequently mutated genes in about 25% of all cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and melanoma. Therefore, oncogenic RAS signaling pathways are fascinated with therapeutic targets for cancer treatment. Extensive efforts have been devoted to the development of effective therapies for RAS mutant cancers.
Although RAS proteins are considered “undruggable” owing to a smooth protein surface structure and high levels of cellular GTP surpassing the nucleotide-binding affinity, some methods to directly inhibit RAS functions have yielded promising efficacy outcomes both in vitro and in preclinical studies, such as chemical inhibitors of mutant KRAS proteins or blockers of RAS dimerization. On the other hand, alternative strategies to directly target RAS have been developed, particularly, targeting key downstream RAS pathway effectors. Extensive evidence has demonstrated a critical role for the RAF-MEK-MAPK and PI3K-AKT cascades in oncogenic RAS signaling. Both pathways are essential in cell proliferation, survival, and other aspects of cell behavior contributing to tumor initiation and development, and have been the focus of intensive therapeutic development efforts for cancer treatment.
This Research Topic aims to present the recent advances in understanding molecular mechanisms underlying activation of RAS functions and RAS downstream effector pathways including MAPK and AKT signaling cascades, and developing promising therapeutic strategies for RAS mutant cancers. The editors expect these articles will provide the cancer research community with fresh and helpful information in basic, translational, and clinical research in the context of cancers mediated by oncogenic RAS signaling pathways. Submissions of Original Research, Reviews, and other article types are welcome, with a focus on (but not limited to) the following themes:
• Identification of novel predictive biomarkers for prognosis of RAS mutant cancers.
• Discovery of new molecular mechanisms regulating RAS localization, dimerization and activation.
• Mechanism studies of oncogenic MAPK and AKT signaling pathways regulating RAS mutant tumor initiation and growth.
• Development of novel therapeutic strategies for treatment of RAS mutant cancers.
• Clinical update on results of targeted therapy focusing on MEK/MAPK inhibitors and PI3K/AKT inhibitors and the future perspectives.
The three RAS genes, including KRAS, NRAS, and HRAS, are among the most frequently mutated genes in about 25% of all cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and melanoma. Therefore, oncogenic RAS signaling pathways are fascinated with therapeutic targets for cancer treatment. Extensive efforts have been devoted to the development of effective therapies for RAS mutant cancers.
Although RAS proteins are considered “undruggable” owing to a smooth protein surface structure and high levels of cellular GTP surpassing the nucleotide-binding affinity, some methods to directly inhibit RAS functions have yielded promising efficacy outcomes both in vitro and in preclinical studies, such as chemical inhibitors of mutant KRAS proteins or blockers of RAS dimerization. On the other hand, alternative strategies to directly target RAS have been developed, particularly, targeting key downstream RAS pathway effectors. Extensive evidence has demonstrated a critical role for the RAF-MEK-MAPK and PI3K-AKT cascades in oncogenic RAS signaling. Both pathways are essential in cell proliferation, survival, and other aspects of cell behavior contributing to tumor initiation and development, and have been the focus of intensive therapeutic development efforts for cancer treatment.
This Research Topic aims to present the recent advances in understanding molecular mechanisms underlying activation of RAS functions and RAS downstream effector pathways including MAPK and AKT signaling cascades, and developing promising therapeutic strategies for RAS mutant cancers. The editors expect these articles will provide the cancer research community with fresh and helpful information in basic, translational, and clinical research in the context of cancers mediated by oncogenic RAS signaling pathways. Submissions of Original Research, Reviews, and other article types are welcome, with a focus on (but not limited to) the following themes:
• Identification of novel predictive biomarkers for prognosis of RAS mutant cancers.
• Discovery of new molecular mechanisms regulating RAS localization, dimerization and activation.
• Mechanism studies of oncogenic MAPK and AKT signaling pathways regulating RAS mutant tumor initiation and growth.
• Development of novel therapeutic strategies for treatment of RAS mutant cancers.
• Clinical update on results of targeted therapy focusing on MEK/MAPK inhibitors and PI3K/AKT inhibitors and the future perspectives.
