KRAS: the forty-year target

KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.

Why here The target.

The RAS-MAPK pathway is the cell's 'divide' relay. A signal at the surface flips RAS on, which passes to RAF, MEK, and ERK, which tell the nucleus to make the cell divide. KRAS and BRAF mutations jam it in the on position.

Why here The pathway and the feedback loops that defeat single agents.

When a cancer depends so completely on one mutated gene that blocking it collapses the tumour.

Why here Why blocking one gene can collapse a tumour.

Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.

Why here The first KRAS drug.

In colorectal cancer, a KRAS blocker alone barely works because the cell turns EGFR up; adding an EGFR antibody stops that.

Why here Why colorectal cancer needs a partner drug.

The first drug that blocks all active RAS variants, approved by the FDA in August 2026 for metastatic pancreatic cancer, where KRAS drives 90% of tumours.

Why here The pan-RAS inhibitor in phase 3 for pancreatic cancer.

Pancreatic cancer is the deadliest common cancer. Almost every tumour carries a KRAS mutation, and for the first time drugs against it are in pivotal trials.

Why here The cancer where this matters most.

Almost every pancreatic cancer shares one of a handful of KRAS mutations. A pre-made vaccine against them could be given to every patient after surgery.

Why here Vaccines against the same mutations.

The most important cancer gene was declared undruggable for 40 years. Then a pocket was found, and now a pan-RAS drug is in phase 3 for pancreatic cancer.

Why here Discovery to speculation in six steps.