Methods of treating cancers
The disclosure relates to methods for treating cancers (e.g., cancers having a BRCA1 and/or BRCA2 mutation(s)) by administering to the subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor.
1. A method for treating a human subject having, or at risk of developing, a cancer, the method comprising administering to the human subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor, wherein the human subject is identified as having a breast cancer gene 1 (BRCA1) and/or breast cancer gene 2 (BRCA2) mutation, and the USP1 inhibitor is administered as a monotherapy.
2. The method of claim 1 , wherein the USP1 inhibitor is
(a) a small molecule inhibitor;
(b) an inhibitory nucleic acid; or
(c) an anti-USP1 antibody or USP1-binding fragment thereof.
3. The method of claim 1 , wherein the cancer is resistant to a PARP inhibitor.
4. The method of claim 3 , wherein the cancer has intrinsic PARP inhibitor resistance, or acquired PARP inhibitor resistance.
5. The method of claim 2 , wherein the small molecule inhibitor is ML323, C527, pimozide, SJB019, or SJB2-043.
6. The method of claim 1 , wherein the cancer is resistant to a cross-linking agent.
7. The method of claim 6 , wherein the cross-linking agent is cisplatin, mitomycin, or busulfan.
8. The method of claim 1 , wherein the cancer is
(a) breast cancer, prostate cancer, pancreatic cancer, fallopian tube cancer, peritoneal cancer, or ovarian cancer;
(b) a basal-like carcinoma or a luminal breast cancer;
(c) a triple-negative breast cancer; or
(d) a high-grade serous ovarian carcinoma.
9. The method of claim 1 , wherein the method comprises identifying the human subject as having
(a) one or more cancer cells that have a BRCA1 mutation;
(b) one or more cancer cells that have a BRCA1 mutation and are PARP inhibitor-resistant; or
(c) one or more cancer cells that have a BRCA2, BRCA1 and BRCA2, or Partner And Localizer of BRCA2 (PALB2) mutation.