| abstract |
This disclosure provides methods of using a checkpoint kinase 1 (Chkl) inhibitor in the treatment of cancer in a subject having at least an intermediate tumor mutational burden (TMB), or a genetic abnormality in one or more particular genes associated with replicative stress. Accordingly, methods of treating cancer in a subject having at least an intermediate tumor mutational burden (TMB-I) are provided. Also provided are methods of treating cancer in a subject having a genetic abnormality in one or more particular genes selected from cell cycle regulation genes, replication stress genes, oncogenic driver mutations and DNA damage response and repair network genes. Methods of selecting subjects for Chkl inhibition therapy are provided. The methods can include administering to the subject an effective amount of a SRA737 compound, in some cases in combination with low dose gemcitabine. |