Biomarkers and methods to determine the efficacy of anti-EGFR antibodies in cancer therapy

摘要

An in vitro method to predict the likelihood of a patient suffering from a wild KRAS colorectal cancer (CRC) where EGFR is expressed, a metastatic colorectal cancer (mCRC), which is a candidate for treatment with an anti-EGFR antibody, respond to treatment with the anti-EGFR antibody, which comprises determining the level of prognostic gene or gene products in a tissue sample obtained from the patient by submitting a sample of the patient's tumor nucleic acids to a PCR, an analysis with RNA series or DNA or a comparable diagnostic tool or apparatus, where (i) a high expression compared to a reference value of a gene selected from ADAMDEC1, BSDC1, C1orf144, CAPZB, CDC42, DHCR7, DNAJC8, ECSIT, EXOSC1O, FADS1 , GBA, GLT25D1, GOSR2, IMPDH1, KLHL21, KPNA6, KPNB1, LSM12, MAN1B1, MIDN, PPAN, SH3BP2, SQLE, SSH3, TNFRSF1B, URM1, ZFYVE26, RGMB, SPIRE2, ABCC5, CDCC2, ABCC5, CDCAM2, ABCC5, CDCAM2, ABCC5, CD5AX5, CDCCA2, ABCC5, CD5AX5, CDCC2 , CEACAM6, ETS2, FMNL2, GPSM 2, HDAC2, JUN, ME3, MED17, MYB, MYC, NEBL, NOSIP, PITX2, POF1B, PPARG, PPP1R14C, PRR15, PSMG1, RAB15, RAB40B, RNF43, RPS23, SLC44A3, SOX4, THEM2, VAV3, ZNF337, ZNF337 KCNK5, KHDRBS3, PGM2L1, STK38 or SHROOM2 or a product thereof is an indication that the patient is likely to respond to treatment, and (ii) a high expression compared to a reference value of a gene selected from C7orf46, CAST , DCP2, DIP2B, ERAP1, INSIG2, KIF21A, KLK6, NGRN, NRIP1, PHGDH, PPP1R9A, QPCT, RABEP1, RPA1, RPL22L1, SKP1, SLC25A27, SLC25A46, SOCS6, TPD52, ZDFHC4, ZDFHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDFHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4, ZDHHC4 , EDEM3, PLLP, RALBP1, SLC4A11, TNFSF15, TPK1, C11orf9, C1QC, cable1, CDK6, EHBP1, EXOC6, EXT1, FLRT3, GCNT2, MTHFS, PIK3AP1, ST3Gal1, TK2, ZDHHC14, ARFGAP3, AXUD1, CAPZB, CHSY1, DNAJB9 , GOLT1B, HSPA5, LEPROTL1, LIMS1, MAPK6, MYO6, PROSC, RAB8B, RAP2B, RWDD2B, SERTAD2, SOCS5, TERF2IP, TIAL1, TIPARP, TRIM8, TSC22D2, TGFA, VAPA or of this one is an indication of this one It is probable that the patient does not respond to the treatment, where the reference value is defined from one or more specific clinical functions or properties and / or a specific expression profile and is obtained from a patient or a group of reference patients where it is expressed a scarce or zero amount of the gene or gene product, where the genes or the prognostic gene products cover at least VAV3 and TGFa.