Identifying cancer drivers

Science ◽  
2021 ◽  
Vol 374 (6563) ◽  
pp. 38-39
Author(s):  
Ran Cheng ◽  
Peter K. Jackson
Keyword(s):  
Cancer Drivers

scholarly journals Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 381
Author(s):  
Bálint Mészáros ◽  
Borbála Hajdu-Soltész ◽  
András Zeke ◽  
Zsuzsanna Dosztányi
Keyword(s):  
Gene Expression Regulation ◽  
Treatment Options ◽  
Intrinsically Disordered Protein ◽  
System Level ◽  
Alternative Mechanism ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Protein ◽  
Cancer Types ◽  
Cancer Drivers

Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.

scholarly journals Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5690
Author(s):  
Sharon Changshan Wu ◽  
Karl Münger
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Clinical Utility ◽  
Cancer Testis Antigens ◽  
Cancer Drivers ◽  
Ct Antigens ◽  
Almost All ◽  
Cancer Testis

Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Due to their expression pattern, they have historically been attractive targets for immunotherapies. A growing number of studies implicate CT antigens in almost all hallmarks of cancer, suggesting that they may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas. However, their role in the pathogenesis of these cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.

scholarly journals Widespread alteration of protein autoinhibition in human cancers

2018 ◽  
Author(s):  
Ashwani Jha ◽  
Jennifer M. Bui ◽  
Dokyun Na ◽  
Jörg Gsponer
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Signal Propagation ◽  
Genetic Alterations ◽  
Missense Mutations ◽  
Pathway Activation ◽  
Tumorigenic Potential ◽  
Significant Enrichment ◽  
Cancer Types ◽  
Cancer Drivers

ABSTRACTAutoinhibition is a prevalent allosteric regulatory mechanism in signaling proteins as it prevents spurious pathway activation and primes for signal propagation only under appropriate inputs. Altered functioning of inhibitory allosteric switches underlies the tumorigenic potential of numerous cancer drivers. However, whether protein autoinhibition is altered generically in cancer cells remains elusive. Here, we reveal that cancer-associated missense mutations and fusion breakpoints are found with significant enrichment within inhibitory allosteric switches across all cancer types, which in the case of the fusion breakpoints is specific to cancer and not present in other diseases. Recurrently disrupted or mutated allosteric switches identify established and new cancer drivers. Cancer-specific mutations in allosteric switches are associated with distinct changes in signaling, and suggest molecular mechanisms for altered protein regulation, which in the case of ASK1, DAPK2 and EIF4G1 were supported by biophysical simulations. Our results demonstrate that autoinhibition-modulating genetic alterations are positively selected for by cancer cells, and that their study provides valuable insights into molecular mechanisms of cancer misregulation.

scholarly journals Novel cancer drivers: mining the kinome

10.1186/gm423 ◽  
2013 ◽  
Vol 5 (2) ◽  
Author(s):  
Andrew V Biankin ◽  
Sean M Grimmond
Keyword(s):  
Cancer Drivers

Tissue specificity in cancer drivers

Science ◽  
2019 ◽  
Vol 363 (6432) ◽  
pp. 1187.14-1189
Author(s):  
Gemma Alderton
Keyword(s):  
Tissue Specificity ◽  
Cancer Drivers

Elucidation of Cancer Drivers Through Comparative Omic Data Analyses

2014 ◽  
pp. 113-147
Author(s):  
Ying Xu ◽  
Juan Cui ◽  
David Puett
Keyword(s):  
Data Analyses ◽  
Cancer Drivers ◽  
Omic Data

Abstract 3588: Computational method to identify non-coding cancer drivers

2017 ◽  
Author(s):  
Eric Minwei Liu ◽  
Priyanka Dhingra ◽  
Alexander M. Fundichely ◽  
Ekta Khurana
Keyword(s):  
Computational Method ◽  
Cancer Drivers

Abstract 388: A benchmark study for identifying cancer drivers in the non-coding part of the genome

2017 ◽  
Author(s):  
Damien Drubay ◽  
Daniel Gautheret ◽  
Stefan Michiels
Keyword(s):  
Benchmark Study ◽  
Cancer Drivers
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