Are there any mutation combinations that cause an increase or decrease of therapeutic (small molecule / antibody / etc) efficacy when they are both mutated together?
Cases in any of the common cancer types... lung/breast/colon etc...
For example:
Increase- Drug A is effective for mutation A in lung cancer. When there is also mutation B, drug is even more effective.
Decrease- Drug A is effective for mutation A in lung cancer. When there is also mutation B, drug's efficacy decreases.
Thank you!
There are few examples for second mutation disabling treatment targeted to another mutation.
Ras activating mutation disables EGFR family targeted monoclonal antibodies or specific kinase inhibitory small molecules (These mutations are on the same signaling pathway).
This knowledge is important to determine why treatments are ineffective in some patients while working in others.
As for increasing effectivity, I wonder if anyone ever bothered to check. It would be interesting to find out.
there is study show that Mutation in both KRAS and STK11 appears to confer increased sensitivity to MEK inhibition in NSCLC cell lines, compared to either mutation
alone.
Germline mutations in MEN1 and BRCA1 genes in a woman with familial multiple endocrine neoplasia type 1 and inherited breast-ovarian cancer syndromes: a case report.(Laura Papi, Domenico Palli, Laura Masi, Anna Laura Putignano, Caterina Congregati, Ines Zanna, Francesca Marini, Francesca Giusti, Ettore Luzi, Francesco Tonelli, Maurizio Genuardi, Maria Luisa Brandi Alberto Falchetti).
Hi, this is a very rare case report that "maybe",could help you, in order to understand how the presence of 2 mutations could play a protective role. Please let me know.
Yep, as answer for both effects.
We started using the term synthetic cytotoxicity for an increased efficacy of drugs/compounds on strains carrying combinations of two or more mutations ( PMID: 24653001). There is a number of examples from the yeast community that scale screening of digenic interactions to include screening on additional drugs present.
There is also the opposite example o combining drugs to increase efficacy (PMID:
22068327).
- Badges
- Science topic
- Similar topics
- Medicine
- Oncology
- Cancer Research
- Cancer Biology