Method For Predicting Therapy Responsiveness In Basal Like Tumors

Abstract

The present invention is related to a method for predicting a clinical response of a patient suffering from or at risk of developing a neoplastic disease towards at least one given mode of treatment, said method comprising the steps of: a) obtaining a biological sample from said patient; b) determining, on a non protein basis, the expression level of at least one gene of interest, said gene being correlated with the Estrogen receptor (ESR) status in the said sample, c) comparing the pattern of expression levels determined in (b) with one or several reference pattern(s) of expression levels; and d) predicting therapeutic success for said given mode of treatment in said patient from the outcome of the comparison in step (c).

What is claimed is: 
     
         1 . A method for predicting a clinical response of a patient suffering from or at risk of developing a neoplastic disease towards at least one given mode of treatment, said method comprising the steps of:
 a) obtaining a biological sample from said patient;   b) determining, on a non protein basis, the expression level of at least one gene of interest, said gene being correlated with the Estrogen receptor (ESR) status in the said sample,   c) comparing the pattern of expression levels determined in (b) with one or several reference pattern(s) of expression levels; and   d) predicting therapeutic success for said given mode of treatment in said patient from the outcome of the comparison in step (c).   
     
     
         2 . The method according to  claim 1 , characterized in that the at least one gene of interest is correlated with a negative Estrogen receptor status. 
     
     
         3 . The method of  claim 1 , characterized in that the at least one gene of interest may be assigned to at least one biological motif selected from the group consisting of
 extracellular matrix degradation,   growth factor signaling,   immune cell infiltration, and/or   basal markers.   
     
     
         4 . The method of  claim 1 , characterized in that the method further comprises the steps of
 e) determining the expression level of at least one gene correlated and/or coexpressed with a receptor from the ErbB-family in the said sample, and/or   f) determining the expression level of at least one gene correlated and/or coexpressed with the Progesteron receptor (PGR) status in the said sample.   
     
     
         5 . The method according to  claim 4 , characterized in that the gene of interest the expression level of which is determined is selected from the group comprising Her-2/neu(=ErbB), MMP7, MMP1, PGR, ESR1, MLPH, IGHM, C-Kit, C-MET and/or EGFR. 
     
     
         6 . The method of  claim 1 , characterized in that at least one mode of treatment for which prediction is sought is a neoadjuvant chemotherapy, a targeted therapy and/or a therapy directed to the inhibition of homologous recombination repair. 
     
     
         7 . The method of  claim 1 , characterized in that an additional mode of treatment for which prediction is sought is a treatment related to the signalling pathway of a receptor from the ErbB-family. 
     
     
         8 . The method of  claim 1 , wherein the expression level is determined by
 a) a hybridization based method,   b) a PCR-based method, particularly a quantitative real-time PCR method,   c) determining the protein level,   d) a method based on the electrochemical detection of particular molecules,   e) an array based method,   f) serial analysis of gene expression (sage) and/or   g) a Planar wave guide based method.   
     
     
         9 . The method of  claim 1 , characterized in that said cancer or neoplastic disease is characterized by a negative Estrogen receptor status, a negative progesterone receptor status and/or a negative Her-2/neu receptor status. 
     
     
         10 . The method of  claim 1 , characterized in that said cancer or neoplastic disease is selected from the group consisting of gynaecological cancers including Breast cancer, Ovarian cancer, Cervical cancer, Endometrial cancer, and/or Vulval cancer. 
     
     
         11 . The method of  claim 1 , characterized in that the expression level of at least one of the said genes is determined with rtPCR (reverse transcriptase polymerase chain reaction) of the gene-related mRNA. 
     
     
         12 . The method of  claim 1 , characterized in that the expression level of at least one of the said ligands of is determined in formalin and/or paraffin fixed tissue samples. 
     
     
         13 . The method  claim 1 , wherein, after lysis, the samples are treated with silica-coated magnetic particles and a chaotropic salt, in order to purify the nucleic acids contained in said sample for further determination. 
     
     
         14 . A kit, comprising at least
 a) a primer pair and/or a probe each having a sequence sufficiently complementary to at least one gene as set forth in any of the aforementioned claims, and/or   b) an antibody directed against an expression product related to at least one gene as set forth in any of the aforementioned claims   
     
     
         15 . A method for correlating the clinical outcome of a patient suffering from or at risk of developing a neoplastic disease, said method comprising the steps of:
 a) obtaining a fixed biological sample from said patient;   b) determining the expression level of at least one gene of interest in said sample according to any of the above methods, and   c) correlating the pattern of expression levels determined in (b) with said patient's data, said data being selected from the group consisting of etiopathology data, clinical symptoms, anamnesis data and/or data concerning the therapeutic regimen.   
     
     
         16 . A nucleic acid molecule, selected from the group consisting of
 a) the nucleic acid molecule presented as SEQ ID NO:1-28   b) a nucleic acid molecule having a length of 4-80 nucleotides, preferably 18-30 nucleotides, the sequence of which corresponds to the sequence of a single stranded fragment of a gene encoding for a ligand and/or receptor selected from the group consisting of ESR1, ESR2, PGR, EGFR, Her-2/neu, ERBB3, ERBB4, MLPH, MMP1, MMP7, MMP9, MMP11, MMP10, MMP13 and immune genes such as IGHM, IGHM, IGHG, IGHD, IGLC, IGLJ, IGLL, IGLV;   c) a nucleic acid molecule that is a fraction, variant, homologue, derivative, or fragment of the nucleic acid molecule presented as SEQ ID NO: 1-28;   d) a nucleic acid molecule that is capable of hybridizing to any of the nucleic acid molecules of a)-c) under stringent conditions;   e) a nucleic acid molecule that is capable of hybridizing to the complement of any of the nucleic acid molecules of a)-d) under stringent conditions;   f) a nucleic acid molecule that is capable of hybridizing to the complement of a nucleic acid molecule of e)   g) a nucleic acid molecule having a sequence identity of at least 95% with any of the nucleic acid molecules of a)-f);   h) a nucleic acid molecule having a sequence identity of at least 70% with any of the nucleic acid molecules of a)-f);   i) a complement of any of the nucleic acid molecules of a)-h), or   j) a nucleic acid molecule that comprises any nucleic acid molecule of a)-i).   
     
     
         17 . The nucleic acid according to  claim 16 , characterized in that the said nucleic acid is selected from the group consisting of DNA, RNA, PNA, LNA and/or Morpholino. 
     
     
         18 . The nucleic acid of  claim 16 , characterized in that it is labelled with at least one detectable marker. 
     
     
         19 . A kit of primers and/or detection probes, comprising at least one of the nucleic acids of  claim 16  and/or their fractions, variants, homologues, derivatives, fragments, complements, hybridizing counterparts, or molecules sharing a sequence identity of at least 70%, preferably 95%. 
     
     
         20 . The kit according to  claim 19 , comprising at least one of the nucleic acid molecules presented as SEQ ID NO: 1-28 and/or their fractions, variants, homologues, derivatives, fragments, complements, hybridizing counterparts, or molecules sharing a sequence identity of at least 70%, preferably 95%, for the detection of at least one gene of interest. 
     
     
         21 . (canceled)