scispace - formally typeset
Open AccessJournal ArticleDOI

KRAS Alleles: The Devil Is in the Detail

Kevin M. Haigis
- 01 Oct 2017 - 
- Vol. 3, Iss: 10, pp 686-697
TLDR
Historical and emerging evidence supports the notion that the specific biology related to each KRAS allele might be exploitable for allele-specific therapy.
Abstract
KRAS is the most frequently mutated oncogene in cancer and KRAS mutation is commonly associated with poor prognosis and resistance to therapy. Since the KRAS oncoprotein is, as yet, not directly druggable, efforts to target KRAS mutant cancers focus on identifying vulnerabilities in downstream signaling pathways or in stress response pathways that are permissive for strong oncogenic signaling. One aspect of KRAS biology that is not well appreciated is the potential biological differences between the many distinct KRAS activating mutations. This review draws upon insights from both clinical and experimental studies to explore similarities and differences among KRAS alleles. Historical and emerging evidence supports the notion that the specific biology related to each allele might be exploitable for allele-specific therapy.

read more

Citations
More filters
Journal ArticleDOI

Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy

TL;DR: The impact of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer is discussed and the challenges and opportunities presented for personalized anticancer therapy, as well as the expanding field of precision immunotherapy are assessed.
Journal ArticleDOI

Role of oncogenic KRAS in the diagnosis, prognosis and treatment of pancreatic cancer.

TL;DR: The role of oncogenic KRAS in the biology, diagnosis, prognosis and treatment of pancreatic cancer is discussed, and KRAS mutation assays could provide important predictive information on tumour progression and recurrence.
Journal ArticleDOI

A model for RAS mutation patterns in cancers: finding the sweet spot.

TL;DR: The idea that there is a narrow window or ‘sweet spot’ in which oncogenic RAS signalling can promote tumour initiation in normal cells is put forward and the evidence that RAS mutation patterns are the product of selection for optimal RAS mutations to achieve the ideal level of signalling is presented.
Journal ArticleDOI

Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction.

TL;DR: The identification of potent and cell-active small-molecule inhibitors which efficiently disrupt the interaction between KRAS and its exchange factor SOS1 are described, a mode of action confirmed by a series of biophysical techniques.
Journal ArticleDOI

Pediatric low-grade glioma in the era of molecular diagnostics

TL;DR: How molecular information can help to further define the entities which fall under the umbrella of pediatric-type low-grade glioma is reviewed and a risk-based stratification system that considers both clinical and molecular parameters to aid clinicians in making treatment decisions is proposed.
References
More filters
Journal ArticleDOI

The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data

TL;DR: The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications.
Journal ArticleDOI

Signatures of mutational processes in human cancer

Ludmil B. Alexandrov, +84 more
- 22 Aug 2013 - 
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Journal ArticleDOI

Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

Ahmet Zehir, +99 more
- 08 May 2017 - 
TL;DR: A large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer are compiled and identified clinically relevant somatic mutations, novel noncoding alterations, and mutational signatures that were shared by common and rare tumor types.
Related Papers (5)