Wild type RAS plays critical roles in both RAS mutant and RAS wild type cancers, in a context-dependent manner. The wild type KRAS isoform largely acts as a tumour suppressor in the context of the cognate mutant KRAS isoform, and its loss facilitates initation and progression as well as metastasis.

The disappearance of RAS clones in the plasma of patients diagnosed with RAS mutations is known as “neo-RAS wild type (wt)” or “RAS conversion”. Current scientific evidence regarding this phenomenon is mixed.

2023年7月24日 · Patients treated with anti-epidermal growth factor receptor (anti-EGFR) will ultimately develop acquired resistance promoted by clonal selection, mainly the emergence of mutations in the MAPK...

New randomized head-to-head trials have shown a possible survival advantage with the preferential choice of targeted anti-epidermal growth factor receptor (anti-EGFR) over anti-vascular endothelial growth factor (anti-VEGF) agents in patients not carrying activating mutations of the RAS proteins.

2023年1月24日 · Background: Metastatic colorectal cancers (mCRC) with wild-type KRAS are often sensitive to anti-EGFR, but occasionally develop resistance within treatment. A major limitation of treatment that selectively target kinase signaling pathways is the emergence of secondary resistance.

Our study indicates that FOLFOX + panitumumab has the major probability to provide an improvement of survival with a good safety profile in patients with RAS WT mCRC with an added value from selection based on sidedness.

2023年3月15日 · In the RAS wild-type population, the current standard of care involves chemotherapy combined with anti-EGFR agents as first-line treatment, followed by a second-line treatment that includes a switch in the chemotherapy backbone combined with bevacizumab.

In non-RAS mutant cancers, wild type RAS is recognized as a mediator of oncogenic signaling due to chronic activation of upstream receptor tyrosine kinases that feed through RAS. Additionally, in the absence of mutant RAS, activation of wild type RAS may drive cancer upon the loss of negative RAS regulators such as NF1 GAP or SPRY proteins.

2021年4月28日 · RAS -mutated tumors were originally thought to proliferate independently of upstream signaling inputs, but we now know that non-mutated wild-type (WT) RAS proteins play an important role in modulating downstream effector signaling and driving therapeutic resistance in RAS -mutated cancers.

Different methods can be used to detect RAS mutations in colorectal cancer specimens, such as mutation-specific real-time polymerase chain reaction (R T-PCR), Sanger sequencing, pyrosequencing, BEAMing technique, next-generation sequencing and …