resistance

Mapped the Fanconi anaemia/BRCA DNA repair pathway and how tumours become resistant to PARP inhibitors.

Used ctDNA to show how colorectal cancers evolve resistance to EGFR antibodies and how that resistance can fade.

After a lung cancer stops responding to an ALK-blocking tablet, finding a change inside the ALK protein itself is good news: it means the cancer still depends on ALK, and a later-generation tablet is likely to work. Finding none means the opposite.

Extra copies of the gene for the androgen receptor. It is almost never present before hormone treatment and is found in about half of prostate cancers that have become resistant to it, which is why the stage the sample was taken at matters more than the result itself.

A change in the part of the androgen receptor that hormone drugs attach to. Depending on which change it is, another hormone the man is already taking can switch the receptor on, or the blocking drug can start behaving as an activating one.

A change in the pocket of the survival protein BCL-2 where venetoclax has to fit. The protein still works and the drug no longer binds it. It can be detected in blood months before the disease starts growing again.

T315I is the gatekeeper mutation in the ABL1 kinase that defeats imatinib, dasatinib, nilotinib and bosutinib. Ponatinib and asciminib are the two drugs approved for it.

A change in the enzyme BTK at the exact point where the drug grips it. The enzyme keeps working and the drug no longer holds, which is the usual reason a BTK inhibitor stops working after it has been working well.

A change in the EGFR protein that removes the anchor point the newest lung cancer pills grip. Whether it can be worked around depends on whether it sits on the same copy of the gene as the earlier resistance change or on the other copy.

T790M is the gatekeeper mutation that lung cancers acquire to escape first- and second-generation EGFR inhibitors. Finding it, in tissue or blood, is the historic gate for osimertinib after an earlier EGFR drug.

ESR1 mutations arise in the oestrogen receptor's ligand-binding domain after aromatase inhibitor treatment, letting the receptor work without oestrogen. They are usually found in a blood test and select the oral SERDs elacestrant and imlunestrant.

HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.

The test result that shows a prostate cancer has changed into a different, faster kind of cancer under hormone treatment. It is made on a biopsy, usually prompted by disease that is growing while the PSA stays flat.