Back to results
US 12,571,050 B2Granted
Method of predicting response to therapy by assessing tumor genetic heterogeneity
AssigneeRoche Sequencing Solutions, Inc.
InventorsAarthi Balasubramanyam, Christine Ju, Xiaoju Ma, Thomas Muley, Felix Herth, Nalin Tikoo, Birgit Wehnl, Liu Xi, Stephanie J. Yaung
Life of this patent
Estimating the term…
Abstract
The invention is a method of predicting response to therapy in a cancer patient by serial sampling the patient's cell-free tumor nucleic acids to determine a change in the number of mutations per amount of plasma.
Claims1
A method of treatment of colorectal cancer (CRC) comprising the steps of:
- (a) providing a blood plasma sample from a CRC patient collected at a first time point during a therapy regimen;
- (b) providing a blood plasma sample from the patient collected at a second time point during the therapy regimen;
- (c) sequencing from the sample at least a portion of each of the biomarkers listed in Table 1 or Table 2 wherein Table 1 is:
- APC
- KRAS
- ABL1
- FGFR3
- JAK3
- RAF1
- BRCA1
- MET
- AKT1
- FLT1
- KDR
- RNF43
- BRCA2
- TP53
- AKT2
- FLT3
- MAP2K1
- TERT promoter
- EGFR
- KIT
- ARAF
- FLT4
- MAP2K2
- TSC1
- ERBB2
- NRAS
- CDK6
- GATA3
- MTOR
- TSC2
- ALK
- PDGFRA
- CSF1R
- GNA11
- NFE2L2
- PTEN
- BRAF
- RET
- CTNNB1
- GNAQ
- NTRK1
- RB1
- DPYD
- ROS1
- DDR2
- GNAS
- PDGFRB
- SMAD4
- AR
- MSH2
- EZH2
- IDH1
- PIK3CA
- SMO
- CCND1
- MSH6
- FGFR1
- IDH2
- PIK3R1
- STK11
- CCND2
- NF2
- FGFR2
- JAK2
- PTCH1
- VHL
- CCND3
- PDCD1LG2
- CDK4
- ESR1
- KEAP1
- UGT1A1
- CD274
- PMS2
- CDKN2A
- FBXW7
- MLH1
- and Table 2 is:
- ABCC5
- CSMD1
- FAT1
- HTR1E
- MAP7D3
- PIK3CA
- SV2A
- ABCG2
- CSMD3
- FBN2
- HTR2C
- MKRN3
- PIK3CG
- T
- ACTN2
- CTNNB1
- FBXL7
- IFI16
- MMP16
- PKHD1L1
- THSD7A
- ADAMTS12
- CTNND2
- FBXW7
- IL7R
- MTX1
- POLE
- TIAM1
- ADAMTS16
- CYBB
- FCRL5
- INSL3
- MYH7
- POM121L12
- TMEM200A
- ARFGEF1
- DCAF12L1
- FOXG1
- ITGA10
- MYT1L
- PREX1
- TNFRSF21
- ASTN1
- DCAF12L2
- FRYL
- ITSN1
- NAV3
- PTPLA
- TNN
- ASTN2
- DCAF4L2
- GBA3
- KCNA5
- NEUROD4
- RALYL
- TNR
- AVPR1A
- DCLK1
- GBP7
- KCNB2
- NFE2L2
- RFX5
- TRHDE
- BCHE
- DCSTAMP
- GJA8
- KCNC2
- NLGN4X
- RIN3
- TRIM58
- BPIFB4
- DDII
- GPR139
- KCNJ3
- NLRP3
- RNASE3
- TRPS1
- C6
- DLGAP2
- GRIA2
- KCTD8
- NMUR1
- ROBO2
- UGT3A2
- C6orf118
- DMD
- GRIK3
- KEAP1
- NOL4
- SEMA5B
- USH2A
- CA10
- DNTTIP1
- GRIN2B
- KIAA1211
- NPAP1
- SLC18A3
- USP29
- CACNA1E
- DOCK3
- GRIN3B
- KIF17
- NROB1
- SLC39A12
- VPS13B
- CDH12
- DSC3
- GRM1
- KIF19
- NRXN1
- SLC6A5
- WBSCR17
- CDH18
- DSCAM
- GRM5
- KLHL31
- NXPH4
- SLC8A1
- WIPF1
- CDH8
- EGFLAM
- GRM8
- KPRP
- NYAP2
- SLITRK1
- WSCD2
- CDH9
- EPHA5
- GSX1
- LPPR4
- OPRD1
- SLITRK4
- ZC3H12A
- CDKN2A
- EPHA6
- HCN1
- LRFN5
- P2RY10
- SLITRK5
- ZFPM2
- CHRM2
- EYS
- HCRTR2
- LRP1B
- PAX6
- SLPI
- ZIC1
- CNTN5
- FAM135B
- HEBP1
- LRRC7
- PCDH15
- SMAD4
- ZIC4
- CNTNAP2
- FAM151A
- HECW1
- LRRTM1
- PDYN
- SOX9
- ZNF521
- CPXCR1
- FAM5B
- HS3ST4
- LRRTM4
- PDZRN3
- SPTA1
- ZSCAN1
- CPZ
- FAM5C
- HS3ST5
- LTBP4
- PGK2
- ST6GALNAC3
- KIT
- CRMP1
- FAM71B
- HTR1A
- MAP2
- PHACTR1
- STK11
- NRAS
- APC
- KRAS
- ALK
- PDGFRA
- MET
- BRAF
- RET
- BRCA1
- BRCA2
- TP53
- DPYD
- EGFR
- ERBB2
- UGT1A1;
- (d) calculating the ratio of the number of mutations detected in the biomarkers to the volume of the samples (MMPM);
- (e) continuing the therapy regimen if the MMPM in the second sample is lower than in the first sample;
- or
- (f) altering the therapy regimen if the MMPM in the second sample is not lower than in the first sample, wherein altering the therapy regimen comprises one or more of increasing the dose of therapy, adding one or more therapeutic agents, and extending the duration of therapy as compared to the non-altered therapy regimen,
- wherein the therapy regimen is selected from treatment with FOLFOXIRI-bevacizumab, treatment with FOLFOX-bevacizumab, capecitabine-bevacizumab and chemoradiation therapy.
279 more elements
Dependencies are inferred from the claim text.