Inhibition of both mutant and wild-type RAS-GTP in KRAS G12C colorectal cancer through cotreatment with G12C and EGFR inhibitors

McFall, Thomas; Trogdon, Michael; Sisk-Hackworth, Laura; Stites, Edward C.

doi:10.1101/845263

Cited by 3 publications

(3 citation statements)

References 57 publications

(140 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ErbB receptor family is composed of four members: ERBB1/EGFR, ERBB2/ HER2, ERBB3/HER3 and ERBB4/HER4, which mainly activate MAPK and PI3K-AKT signaling pathways. High EGFR promotes RAFi resistance in CRC, lung, melanoma and thyroid cancer cells by rapid feedback activation of EGFR signaling [113][114][115][116][117], and determines the G12Ci refractory state in KRAS G12C cancers [33,34,[118][119][120]. However, EGFR does not seem to be the dominant driver of MEKi resistance in PDAC.…”

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Conquering oncogenic KRAS and its bypass mechanisms

Hou¹,

Wang²

2022

Theranostics

View full text Add to dashboard Cite

Aberrant activation of KRAS signaling is common in cancer, which has catalyzed heroic drug development efforts to target KRAS directly or its downstream signaling effectors. Recent works have yielded novel small molecule drugs with promising preclinical and clinical activities. Yet, no matter how a cancer is addicted to a specific target -cancer's genetic and biological plasticity fashions a variety of resistance mechanisms as a fait accompli, limiting clinical benefit of targeted interventions. Knowledge of these mechanisms may inform combination strategies to attack both oncogenic KRAS and subsequent bypass mechanisms.

show abstract

Section: Receptor Tyrosine Kinasesmentioning

confidence: 99%

Conquering oncogenic KRAS and its bypass mechanisms

Hou¹,

Wang²

2022

Theranostics

View full text Add to dashboard Cite

show abstract

“…Evidence for this possibility comes from statins, HMG-CoA reductase inhibitors, which inhibit the mevalonate pathway by directly interfering with farnesylation processes [188]. In vitro trials using CRC cells did show a synergis-tic effect when statins and EGFR monoclonal antibody were combined [189], but their use in clinical trials did not restore the sensitivity to cetuximab in patients harbouring RAS mutations [190].…”

Section: Anti-ras Strategies: a New Ally For Improving Current Efgr-targeted Therapies?mentioning

confidence: 99%

Ras Family of Small GTPases in CRC: New Perspectives for Overcoming Drug Resistance

Río-Vilariño

Puerto‐Nevado

García‐Foncillas

et al. 2021

Cancers

View full text Add to dashboard Cite

Colorectal cancer remains among the cancers with the highest incidence, prevalence, and mortality worldwide. Although the development of targeted therapies against the EGFR and VEGFR membrane receptors has considerably improved survival in these patients, the appearance of resistance means that their success is still limited. Overactivation of several members of the Ras-GTPase family is one of the main actors in both tumour progression and the lack of response to cytotoxic and targeted therapies. This fact has led many resources to be devoted over the last decades to the development of targeted therapies against these proteins. However, they have not been as successful as expected in their move to the clinic so far. In this review, we will analyse the role of these Ras-GTPases in the emergence and development of colorectal cancer and their relationship with resistance to targeted therapies, as well as the status and new advances in the design of targeted therapies against these proteins and their possible clinical implications.

show abstract

“…Recently, a preclinical study has suggested synergism between cetuximab and AMG 510 in KRAS G12C mutated CRC, implying that the combination could be explored as an alternative approach. 79 Meanwhile, one can explore the upcoming results of different KRAS G12C inhibitors, as well as mutant-specific agents targeting more common variants such as KRAS G12D or G12V. 80 treating patients with rare genetic alterations Other than BRAF or HER2, even rarer genetic alterations in mCRC are now being considered as actionable targets.…”

Section: Strategies Targeting Braf-mutant Crcmentioning

confidence: 99%

Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer

Kim

2020

ESMO Open

View full text Add to dashboard Cite

Over the last few decades, molecularly targeted agents have been used for the treatment of metastatic colorectal cancer. They have made remarkable contributions to prolonging the lives of patients. The emergence of several biomarkers and their introduction to the clinic have also aided in guiding such treatment. Recently, next-generation sequencing (NGS) has enabled clinicians to identify these biomarkers more easily and reliably. However, there is considerable uncertainty in interpreting and implementing the vast amount of information from NGS. The clinical relevance of biomarkers other than NGS are also subjects of debate. This review covers controversial issues and recent findings on such therapeutics and their molecular targets, including VEGF, EGFR, BRAF, HER2, RAS, actionable fusions, Wnt pathway and microsatellite instability for comprehensive understanding of obstacles on the road to precision oncology in metastatic colorectal cancer.

show abstract

Inhibition of both mutant and wild-type RAS-GTP in KRAS G12C colorectal cancer through cotreatment with G12C and EGFR inhibitors

Cited by 3 publications

References 57 publications

Conquering oncogenic KRAS and its bypass mechanisms

Conquering oncogenic KRAS and its bypass mechanisms

Ras Family of Small GTPases in CRC: New Perspectives for Overcoming Drug Resistance

Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer

Contact Info

Product

Resources

About