Abstract: The present disclosure provides methods for treating cancer comprising administering one or more therapeutic agents for manipulation of a target gene (e.g., protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1)), wherein the cancer has a mutation in, an altered (e.g., increased or decreased) expression level and/or an altered activity of a biomarker. Provided herein are methods for identifying biomarkers of the disclosure that form a synthetic lethal pair with a target gene (e.g., PKMYT1).

Abstract: Methods and compositions for treating cancer are disclosed herein. The methods may comprise use of therapeutically effective amounts of one or more therapeutic agents to cause a difference in expression or activity of protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1) in cancer cells that are deficient in protein phosphatase 2 regulatory subunit B alpha (PPP2R2A).

Abstract: The present disclosure provides methods for treating cancer comprising administering one or more therapeutic agents for manipulation of a target gene (e.g., protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1)), wherein the cancer has a mutation in, an altered (e.g., increased or decreased) expression level and/or an altered activity of a biomarker. Provided herein are methods for identifying biomarkers of the disclosure that form a synthetic lethal pair with a target gene (e.g., PKMYT1).

Abstract: The present disclosure provides methods for treating cancer comprising administering one or more therapeutic agents for manipulation of a target gene (e.g., protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1)), wherein the cancer has an altered (e.g., increased or decreased) expression level and/or activity of a biomarker. Provided herein are methods for identifying biomarkers of the disclosure that form a synthetic lethal pair with a target gene (e.g., PKMYT1).

Abstract: The present disclosure provides lethal gene pair targets for cancer treatment, along with methods and compositions for regulating their expression and activity. Gene pairs disclosed herein include tyrosine kinase genes (e.g., SRC, RON, and YES). Also provided are methods and compositions for regulating tyrosine kinase activity, including RON specific pyrazole benzamide inhibitors and methods for gene regulation.