RE:G12D/G12V KRAS mutation in PC & CRC patients respond to PelaThe KRAS G12D mutation is present in more than one in three pancreatic cancers, about one in ten colorectal cancers, and in several other cancer types. The KRAS protein normally acts like an on–off switch. In response to certain signals, it becomes activated and tells the cell to grow and divide. When the signals are no longer present, it turns off. However, some mutant forms of KRAS, such as KRAS G12D, remain active even in the absence of growth signals, leading to uncontrolled cell growth.
The KRAS G12D mutation is present in more than one in three pancreatic cancers, about one in ten colorectal cancers, and in several other cancer types.
ONCYs pelareorep is able turn off KRAS G12D and in so doing reverse the immunospressive tumor microenvironment (TME) in advance of the addition of immune checkpoint inhibition such as atezolizumab. https://stockhouse.com/companies/bullboard?symbol=t.onc&threadid=35639972
Mutations in both KRAS and TP53 genes are found in around 80% and 70% of all human pancreatic cancers respectively.
Mutant KRAS, found in 95% of pancreatic cancers, leads to an activated protein that aberrantly triggers many downstream signaling pathways. Mutant TP53 results in the loss of the proteins’ tumor suppressor function, leaving the mutant protein capable of fueling additional oncogenic processes, such as metastasis.
ONCYs pelareorep demonstrates to be effective in the knockdown of both KRAS (G12D/G12V KRAS mutations) and p53 gene activity, and ultimately effective in the treatment of pancreatic and GI cancers
More than half the CRC patients that responded to pelareorep had either a G12V or a G12D mutation (exon 2, codon 12, KRAS gene).
"With Revolution Medicines initiating dosing in the first-in-human study of its KRAS G12D inhibitor RMC-9805, the industry pipeline now comprises six clinical-stage projects with this modality. If the KRAS G12C space, now featuring the approved drugs Lumakras from Amgen and Krazati from Mirati, fast became crowded, then that targeting KRAS G12D-driven tumours might follow suit, given that G12D is said to be the most common driver of RAS-addicted human cancers. Revolution’s phase 1 study is enrolling patients with G12D-driven cancers, and is designed to inform the phase 2 dose; the company, which recently acquired EQRX for the latter’s cash balance, is also developing projects targeting various other KRAS mutations, in addition to assets with companion mechanisms including SHP2 and SOS1. The competition, meanwhile, includes Mirati’s MRTX1133 and Astellas’s degrader project ASP3082, as well as engineered T-cell receptor approaches at the NCI (this had been in Kite’s pipeline, so Gilead presumably has some rights over it), Medigene and the private companies Affini-T and Anocca." https://www.oncologypipeline.com/apexonco/revolution-next-kras-battleground November 2023 - AstraZeneca has taken an exclusive worldwide license to a KRASG12D mutation drug Roche/Chugai’s pan-RAS inhibitor LUNA18 has already completed a dose-ranging study, while Quanta’s multi-KRAS inhibitor QTX3034 is in preclinical development. https://pharmaphorum.com/news/astrazeneca-joins-kras-push-cancer-chinese-deal