Methods of treating cancers containing fusion genes
The present invention relates to methods of treating cancer patients carrying one or more specific fusion genes. It is based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity and the use of tyrosine kinase inhibitors targeting MAN2A1-FER in a cancer other than prostate, for example hepatocellular cancer, led to dramatic improvement of survival of animals xenografted with the cancer.
1 . A method of treating a subject in need thereof, wherein the method comprises performing one or more of administering a therapeutically effective amount of an inhibitor specific for a fusion gene, a cryotherapy, a radiation therapy, a chemotherapy, a hormone therapy, a high-intensity focused ultrasound and frequent monitoring to achieve an anti-neoplastic effect in the subject, wherein the subject does not have prostate cancer,
wherein the subject has at least one condition selected from the group consisting of a premalignant condition, a neoplastic condition, a cancer, and combination thereof,
wherein the subject has at least one fusion gene selected from the group consisting of a Phosphatase and Tensin Homolog gene fused with a Nucleolar And Coiled-Body Phosphoprotein 1 gene (PTEN-NOLC 1 ), a Solute Carrier Family 45, Member 2 gene fused with an Alpha-methylacyl-CoA Racemase gene (SLC45A2-AMACR) and combinations thereof,
wherein the inhibitor for the PTEN-NOLC1 fusion gene comprises an EGFR inhibitor, a FER inhibitor, or a siRNA targeting the PTEN-NOLC1 fusion gene, and
wherein the inhibitor for the SLC45A2-AMACR fusion gene comprises a racemase inhibitor and/or an AMACR inhibitor, or a siRNA targeting the SLC45A2-AMACR fusion gene.
2 . The method of claim 1 , wherein the subject has a pre-malignant or neoplastic condition.
3 . The method of claim 1 , wherein the subject has a cancer.
4 . The method of claim 3 , wherein the cancer is breast cancer, liver cancer, lung cancer, non-small cell lung cancer, cervical cancer, endometrial cancer, pancreatic cancer, ovarian cancer, gastric cancer, thyroid cancer, colorectal cancer, sarcoma, diffuse large B-cell lymphoma, or esophageal adenocarcinoma.
5 . The method of claim 3 , wherein the cancer is not lung adenocarcinoma, glioblastoma multiforme or hepatocellular carcinoma.
6 . The method of claim 1 , wherein the fusion gene is detected by FISH analysis or by reverse transcription polymerase chain reaction.