New York, New York-based biopharmaceutical company Bristol-Myers Squibb (NYSE: BMY) has released new data from a cohort of the phase 2 CheckMate -142 trial evaluating Opdivo (nivolumab) and Yervoy (ipilimumab) for the treatment of patients with DNA mismatch repair
deficient or microsatellite instability-high (MSI-H) metastatic colorectal cancer, the company said.
Bristol-Myers Squibb announced new data from a cohort of the phase 2 CheckMate -142 trial evaluating Opdivo and Yervoy for the treatment of patients with DNA mismatch repair
deficient or microsatellite instability-high metastatic colorectal cancer.
Mutations of tumor suppressor genes TP53 (4) and pl6 (5); dysregulation of proto-oncogenes EGF, (6) EGFR, (7) TGF, (8) and HER2 (9); and loss of DNA mismatch repair
function10,11 have all been described.
Anti-PD-1 antibodies are generally more effective in patients with a high frequency of microsatellite instability (MSI), a biomarker that results in dysfunctional DNA mismatch repair
, and less effective in other patients.
Bristol-Myers Squibb Company today announced interim data from CheckMate -142, a Phase 2, multi-cohort trial evaluating Opdivo (nivolumab) monotherapy or in combination with Yervoy (ipilimumab) for the treatment of patients with DNA mismatch repair
deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC).
1] Such DNA damage can be corrected by some DNA repair mechanisms such as base excision repair (BER), nucleotide excision repair (NER), double strand break repair (DSBR) and, DNA mismatch repair
(DMR) which play a crucial role in maintenance of genomic integrity.
Such instabilities result from deficient function of DNA mismatch repair
(MMR) genes, thus indicating a tendency toward increased genetic mutations [6-8].
Tumor biology studies established new chemoprevention for familial adenomatous polyposis syndrome and universal tumor screening guidelines based on DNA mismatch repair
mutations and microsatellite instability for colorectal cancer in patients with Lynch syndrome.
Modrich's conclusion was that DNA mismatch repair
is a natural process that corrects mismatches that occur when DNA is copied, recognizing the defect strand by its unmethylated state.
coli) (MLH1), (4) DNA mismatch repair
protein Msh2 (MSH2), mutS homolog 6 (MSH6), mismatch repair endonuclease PMS2 (PMS2), and epithelial cell adhesion molecule (EPCAM), such as occurs in patients with Lynch syndrome, for whom more than 90% of colon cancers test MSI positive (1, 2).
Orans has extensive experience in DNA mismatch repair
in hereditary colon cancer, bacterial fitness and pathogenesis in infectious disease, and brings expertise in using macromolecular crystallography to study the structural biology and biochemistry of proteins and nucleic acids.
Another autosomal-dominant disorder, hereditary nonpolyposis colorecstal cancer (HNPCC) syndrome arises as a result of a genetic defect in DNA mismatch repair