Predictive biomarker for hypoxia-activated prodrug therapy
CYP2W1 levels are predictive of the probability that a cancer patient will respond favorably to cancer therapy involving administration of a hypoxia-activated achiral phosphoramidate mustards.
1. A method for treating cancer overexpressing CYP2W1 RNA or protein in a patient, comprising the steps of determining that a CYP2W1 RNA or protein level in a cancer sample isolated from said patient exceeds a predetermined level and administering to said patient a hypoxia-activated prodrug, wherein the hypoxia-activated prodrug comprises (2-bromoethyl)({[(2-bromoethyl)amino][(2-nitro-3-methylimidazol-4-yl)methoxy]phosphoryl})amine (TH-302) and wherein the cancer patient is suffering from gall bladder cancer or non-small cell lung cancer.
2. The method according to claim 1 , wherein the CYP2W1 RNA level is determined relative to a control sample as Log 2 value with the predetermined value of 5.0 Log 2.
3. The method according to claim 1 , wherein CYP2W1 RNA or protein measured level exceeds the predetermined level in gall bladder PDX tumor model GL1208, or a non-small cell lung cancer PDX model selected from the group of LU1304, LU2505, LU1380, LU0357, LU1235 and LU0387.
4. The method of claim 1 , wherein the hypoxia-activated prodrug is administered in an amount of 100 mg/m 2 to 700 mg/m 2 to the patient in need of cancer therapy.
5. The method of claim 1 , wherein the patient sample is one or more of a serum sample, plasma sample, whole blood sample, pancreatic juice sample, tissue sample, tumor sample or tumor lysate.
6. The method of claim 1 , wherein the CYP2W1 RNA level is determined by a method comprising PCR, qRT-PCR, multiplex qPCR or in-situ hybridization, or the CYP2W1 protein level is determined by a method comprising immunohistochemistry, histochemistry, western blot, FACS, immunofluorescence staining or Luminex technology.