I am not a biochemist but I would go with the PCR also. IHC attempts to detect proteins by using antibodies. But if the antibody is not completely specific to the variant, there could be errors. If they get a good genome sample, however, that should be definitive.
Am I to understand that both folfox and folfiri have failed? Have you looked into clinical trials? There are several trying to apply immunotherapy with something else to make it work for "cold" tumors (which most CRC is).
I don't think anything has come out for preliminary results of these pan-KRAS inhibitors. Supposedly they also have specific KRAS inhibitors, as does Mirati, but those are all currently for G12C which is mainly seen in lung cancer, and is fairly rare in colorectal. Mirati supposedly has a G12D one ready to start in trials soon but only at MD Anderson. (My DH is G12D.)
I am also extremely interested in a CXCR2 (chemokine receptor 2) inhibitor+checkpoint inhibitor. Chemokines are known to play a major role in KRAS-mutated cancers in particular.
There are also several vaccine+immunotherapy trials. Cancer vaccines are always five years away from working but we may have more accumulated knowledge now. Both Pfizer and Moderna are working on or have mRNA vaccines for KRAS. There are some virus-based vaccines as well.
KRAS is usually associated with a lower TMB overall for MSS.
Preliminary results did come out for the Mirati G12C inhibitor. It was pretty effective for NSCLC but not very effective at all on its own for CRC. The company said this was "expected" because CRC is "more biologically complex" than lung cancer. I don't know why that is the case but it's an issue. Maybe more complex immune involvement, perhaps a different cascade of mutations. Also the same mutation can have different effects in different cancers/tissues. Pancreatic is usually adenocarcinoma and is nearly always KRAS mutated (something like 90%) with G12D the most common, but it's still more aggressive than CRC with KRAS G12D.
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