Recent Patents and Advances in Genomic Biomarker Discovery for Colorectal Cancers
Colorectal cancer (CRC) is the third most common cancer in the world. Early diagnosis of colorectal cancer is the key to reducing the death rate of CRC patients. Predicting the response to current therapeutic modalities of CRC will also have a great impact on patient care. This review summarizes recent advances and patents in biomarker discovery in CRC under five major categories; including genomic changes, expression changes, mutations, epigenetic changes and microRNAs. The interesting patents include: 1) a patent for a method to differentiate normal exfoliated cells from cancer cells based on whether they were subjected to apoptosis and DNA degradation; 2) A model (PM-33 multiple molecular marker model) based on expression changes of up-regulation of the MDM2, DUSP6, and NFl genes down-regulation of the RNF4, MMD and EIF2S3 genes, which achieved an 88% sensitivity, and an 82% specificity for CRC diagnosis; 3) gene mutations in PTEN, KRAS, PIK3CA for predicting the response to anti-EGFR therapies, a common drug used for CRC treatment; 4) patents on epigenetic changes of ITGA4, SEPT9, ALX4, TFAP2E FOXL2, SARM1, ID4 etc. and many key miRNAs. Finally, future directions in the fields were commented on or suggested, including the combination of multiple categories of biomarkers and pathway central or network-based biomarker panels.
Keywords: Colorectal cancer, patent, biomarker, diagnosis, prognosis, miRNA, epigenetic, mutation, Genomic Biomarker, CRC, expression changes, epigenetic changes, MDM2, DUSP6, NFl genes, ITGA4, 9-Sep, ALX4, TFAP2E, FOXL2, SARM1, tomography (CT) colongraphy, computed, flexible sigmoidoscopy, double contrast barium enema, fecal occult blood testing (FOBT), guaiac based fecal blood tests (gFOBT), iFOBT, RNF4, MMD, RNPCl, TCFL5, C20orf24, AURKA/STK6, FGFR2, guanylyl, cyclase C (GCC), EIF2S3, ADRMl, KRAS mutations, ITGA4 [integrin, alpha 4 (antigen CD49D)], H19 and IGF2, CDKN2A, CXX1, TIMP2, GRO3, RAB32, DMRTB1, CTAG2, BNIP3, ZNF655, KRAS, PI3KCA, MKK4, Epigenomics, hypermethylation, SNRPN, CHD5, ARMCX2, RASGRF2, reproducible, EAXCT, non-redundant
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