Methods for assessing cisplatin resistance, disease progression, and treatment efficacy in ovarian cancer

Abstract

The invention provides methods for predicting whether an ovarian cancer patient's tumor will be resistant to chemotherapy. The invention also provides methods for monitoring the effectiveness of treatment, particularly a chemotherapeutic treatment, in a patient treated for ovarian cancer. The invention further provides methods for treating ovarian cancer, by reducing chemotherapeutic drug resistance in said cells. In addition, the invention provides methods of screening compounds to identify tumor cell growth inhibitors in tumor cells resistant to conventional chemotherapeutic treatment regimes.

1 . A method of detecting a cisplatin resistant tumor in an ovarian cancer patient, said method comprising:
 (a) obtaining an ovarian cancer tumor sample taken from the patient;   (b) measuring the gene expression level of a genetic marker in the patient's tumor sample; and   (c) comparing the expression level of said genetic marker in the ovarian cancer tumor sample taken from the patient and a cisplatin responsive ovarian tumor sample,   wherein the genetic marker is S100A10, S100A11, Calpain 2, SPARC, MetAP2, KLK6, ARA9, Calponin 2, RNPS1, eIF5, eIF2Bε, HSF2, WDR1, Fused toes, NM23D, ADAR1, Grancalcin, NBR1, SAPK/Erk1, zinc finger protein-262 MYM, HYA22, MRPL4, Vinexin β, G-CSFR, IGFBP-7, FAST kinase, TESK2, SRB1, KIAA0082, MPP10, HMT1, NAIP, eEF1ε, RAB22A, NCOR2 or MT1.   
     
     
         2 . A method of assessing whether an ovarian cancer patient's tumor is resistant to cisplatin comprising the steps of:
 (a) obtaining an ovarian cancer tumor sample taken from the patient;   (b) measuring the gene expression level of a genetic marker in the patient's tumor sample;   (c) comparing the expression level of said genetic marker in the ovarian cancer tumor sample taken from the patient and a cisplatin responsive ovarian tumor sample; and   (d) determining that the ovarian cancer patient's tumor is resistant to cisplatin when the expression level of said genetic marker in the ovarian cancer tumor sample taken from the patient is at least 1.2-fold greater than the expression level of said genetic marker in the cisplatin responsive ovarian tumor sample,   wherein the genetic marker is S100A10, S100A11, Calpain 2, SPARC, MetAP2, KLK6, ARA9, Calponin 2, RNPS1, eIF5, eIF2Bε, HSF2, WDR1, Fused toes, NM23D, ADAR1, Grancalcin, NBR1, SAPK/Erk1, zinc finger protein-262 MYM, HYA22, MRPL4, Vinexin β, G-CSFR, IGFBP-7, FAST kinase, TESK2, SRB1, KIAA0082, MPP10, HMT1, NAIP, eEF1ε, RAB22A, NCOR2 or MT1.   
     
     
         3 . The method of  claim 2 , further comprising the step of measuring expression levels of a control gene, and normalizing the expression levels of the genetic marker according to the expression levels of the control gene. 
     
     
         4 . The method of  claim 2 , wherein the expression levels of the genetic marker are measured relative to expression levels of a control gene. 
     
     
         5 . The method of  claim 4 , wherein the control gene is the 18S RNA gene. 
     
     
         6 . The method of  claim 2 , wherein the expression levels are measured using a Northern blot. 
     
     
         7 . The method of  claim 2 , wherein the expression levels are measured using DNA amplification techniques. 
     
     
         8 . The method of  claim 7 , wherein the DNA amplification techniques comprise PCR, RT-PCR, or quantitative real-time RT-PCR (qPCR). 
     
     
         9 . The method of  claim 7 , wherein the DNA is amplified using oligonucleotide primers comprising the nucleotide sequences according to SEQ ID NOs: 16, 22-58, 62-63, or 109-134. 
     
     
         10 . The method of  claim 9 , wherein the primers comprise the nucleotide sequences according to SEQ ID NO: 17 and SEQ ID NO: 18. 
     
     
         11 . The method of  claim 9 , wherein the primers comprise the nucleotide sequences according to SEQ ID NO: 14 and SEQ ID NO:16, or SEQ ID NO: 15 and SEQ ID NO: 62. 
     
     
         12 . The method of  claim 7 , wherein the amplified DNA sequence comprises SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3. 
     
     
         13 . The method of  claim 7 , wherein the amplified DNA sequence comprises SEQ ID NO:7, SEQ ID NO:8, or SEQ ID NO:9. 
     
     
         14 . A method of treating ovarian cancer in a patient, said method comprising:
 (a) obtaining an ovarian cancer tumor sample taken from the patient;   (b) measuring the gene expression level of a genetic marker in the patient's tumor sample;   (c) comparing the expression level of said genetic marker in the ovarian cancer tumor sample taken from the patient and a cisplatin responsive ovarian tumor sample; and   (d) determining that the ovarian cancer patient's tumor is not resistant to cisplatin when the expression level of said genetic marker in the ovarian cancer tumor sample taken from the patient is not at least 1.2-fold greater than the expression level of said genetic marker in the cisplatin responsive ovarian tumor sample; and   (e) administering an effective amount of cisplatin to the ovarian cancer patient;   wherein the genetic marker is S100A10, S100A11, Calpain 2, SPARC, MetAP2, KLK6, ARA9, Calponin 2, RNPS1, eIF5, eIF2Bε, HSF2, WDR1, Fused toes, NM23D, ADAR1, Grancalcin, NBR1, SAPK/Erk1, zinc finger protein-262 MYM, HYA22, MRPL4, Vinexin β, G-CSFR, IGFBP-7, FAST kinase, TESK2, SRB1, KIAA0082, MPP10, HMT1, NAIP, eEF1ε, RAB22A, NCOR2 or MT1.