RAS Mutations in Human Cancers: Roles in Precision Medicine.

  title={RAS Mutations in Human Cancers: Roles in Precision Medicine.},
  author={Avaniyapuram Kannan Murugan and Michele Grieco and Nobuo Tsuchida},
  journal={Seminars in cancer biology},

Emerging RAS-directed therapies for cancer

A review summarizes the diverse approaches that have been taken to RAS inhibition and then focuses on the most recent developments in direct inhibition of KRAS(G12C), which carries much promise.

K-RAS4A: Lead or Supporting Role in Cancer Biology?

It is concluded that a significant body of evidence supports a leading role rather than a supporting (or secondary) role for K-RAS4A in cancer biology.

The RASSF1A Tumor Suppressor Binds the RasGAP DAB2IP and Modulates RAS Activation in Lung Cancer

It is demonstrated that RASSF1A upregulates DAB2IP protein levels in NSCLC cells and presents the first mechanistic evidence for control of RAS activation by RASSf1A.

A Driver Never Works Alone—Interplay Networks of Mutant p53, MYC, RAS, and Other Universal Oncogenic Drivers in Human Cancer

This review focuses on representative examples of the interaction of major oncogenic drivers with one another and selects the drivers with the highest frequency of known activation in human neoplasia.

Targeting RAS in neuroblastoma: Is it possible?

Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges

The mutations and functions of KRAS in human tumors are outlined and then indirect and direct approaches to shut down the oncogenic KRAS network are analyzed, including mechanistic principles, clinical features, and strategies for overcoming primary or secondary resistance to KRAS-G12C blockade.

Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?

The potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC are reviewed, which potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy.

Targeting Mutated KRAS Genes to Treat Solid Tumours.

The importance of mutant KRAS in solid tumours, prior attempts at inhibiting mutantKRAS, and the current promising targeted agents being investigated in clinical trials are summarized, along with future challenges.

Targeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy

The recent major findings in the study of the RAS/RAF/MEK/ERK signaling cascade are summarized, particularly with respect to the impact on clinical cancer therapy.



ras oncogenes in human cancer: a review.

  • J. Bos
  • Biology, Medicine
    Cancer research
  • 1989
It appeared that ras gene mutations can be found in a variety of tumor types, although the incidence varies greatly and some evidence that environmental agents may be involved in the induction of the mutations.

Kirsten Ras* oncogene: Significance of its discovery in human cancer research

The historical background and experimental studies that led to the discovery of Kirsten Ras as an oncogene, the role of mutated KRAS in human carcinogenesis, and recent therapeutic studies of cancer cells with KRAS mutations are addressed.

Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome.

Molecular modeling studies showed that different conformations imposed by mutant KRas may lead to altered association with downstream signaling transducers, and implies that therapeutic interventions may need to take into account the specific mutants expressed by the tumor.

Somatic activation of the K-ras oncogene causes early onset lung cancer in mice

It is shown that mice carrying mutations in the tumour suppressor gene p53 were highly predisposed to a range of tumour types, predominantly early onset lung cancer.

RAS Interaction with PI3K: More Than Just Another Effector Pathway.

Current knowledge about how RAS regulates one of its best-known effectors, PI3K, is summarized and combined therapy with another RAS-regulated pathway such as RAF/MEK/ERK may be the most effective way to treat cancer, at least in animal models mimicking the human disease.

Dampening oncogenic RAS signaling

Mechanisms by which RAS signaling is dysregulated in cancer are revealed and newly identified therapeutic strategies with the potential to target oncogenic RAS-MAPK signaling are highlighted.

Therapeutic strategies for targeting ras proteins.

Drug combinations that target multiple points within the Ras signaling network are likely to be necessary to achieve substantial clinical benefit and unbiased screens for genes necessary for Ras transformation have revealed new potential targets and have added to the understanding of Ras cancer biology.

Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo.

The data, which demonstrate strong selective pressure to overcome the defective activation of PI3 kinase/Akt and Raf/MEK/ERK, implicate both Ras effector pathways as drivers of aberrant growth in T-ALL and further suggest that leukemia cells will deploy multiple mechanisms to develop resistance to targeted inhibitors in vivo.

Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung.

It is concluded that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer.