What is RAS in cancer?
Ras genes encode proteins that can cause cancer (or become oncogenic) when mutated. All Ras proteins are GTPases which act as molecular switches in the cell, regulating signaling pathways and other interactions.
Is KRAS and Ras the same?
The KRAS gene is in the Ras family of oncogenes, which also includes two other genes: HRAS and NRAS. These proteins play important roles in cell division, cell differentiation, and the self-destruction of cells (apoptosis).
Is Ras a proto oncogene?
The ras proto-oncogene in mammalian cells encodes a 21-kilodalton guanosine triphosphate (GTP)-binding protein. This gene is frequently activated in human cancer.
Why is RAS important in cancer?
The main members of the RAS gene family— KRAS, HRAS, and NRAS—encode proteins that have a pivotal cytoplasmic role in cell signaling. When RAS genes are mutated, cells grow uncontrollably and evade death signals. RAS mutations also make cells resistant to some available cancer therapies.
How is RAS involved in tumor formation?
The oncogenic versions of Ras contain point mutations which block the GTPase activity in the presence and absence of GAP. This process in turn inhibits the cycling of the switch and leads to the accumulation of Ras in the active form and contributes to tumor formation.
What is the function of Ras?
Ras proteins function as binary molecular switches that control intracellular signaling networks. Ras-regulated signal pathways control such processes as actin cytoskeletal integrity, cell proliferation, cell differentiation, cell adhesion, apoptosis, and cell migration.
What is a RAS mutation?
Why is RAS so important?
RAS proteins are important for normal development. Active RAS drives the growth, proliferation, and migration of cells. In normal cells RAS receives signals and obeys those signals to rapidly switch between the active (GTP) form and the inactive (GDP form) states.
How is Ras involved in tumor formation?
Is ras an oncogene or tumor suppressor?
The ras oncogene and the p53 tumor-suppressor gene will be used as examples of molecular targets of chemical carcinogens. Activated ras genes predominate as the family of oncogenes to be isolated from solid tumors that are induced by chemicals in laboratory animals.
Why are Ras targeted therapies called undruggable?
RAS-targeted therapies: is the undruggable drugged? RAS (KRAS, NRAS and HRAS) is the most frequently mutated gene family in cancers, and, consequently, investigators have sought an effective RAS inhibitor for more than three decades. Even 10 years ago, RAS inhibitors were so elusive that RAS was termed ‘undruggable’.
Are there any effective therapies for Ras-driven oncogenesis?
For more than three decades, development of effective therapeutics to inhibit RAS -driven oncogenesis has eluded the field and RAS was thought to be ‘undruggable’. However, a clinically approved mutant selective KRAS therapy is now within sight as the FDA has granted an allele-specific covalent inhibitor, AMG 510, Fast Track designation 1.
Are there any Ras targeted therapies for lung cancer?
AMG 510 binds to KRAS-G12C, the RAS mutatant most commonly found in non-small-cell lung tumours. This successful inhibition of KRAS-G12C, has given hope that a range of mutant RAS allele-specific targeted therapies could become therapeutically tractable.
Which is the best treatment for Ras mutant tumours?
Currently, direct inhibition of mutant RAS through allele-specific inhibitors provides the best therapeutic approach. Therapies that target RAS-activating pathways or RAS effector pathways could be combined with these direct RAS inhibitors, immune checkpoint inhibitors or T cell-targeting approaches to treat RAS-mutant tumours.