Combined treatment with APR-246 and platinum or other DNA-damaging drugs could allow dramatically improved therapy of a wide range of therapy refractory p53 mutant tumors.
Selective inhibitors of the kinases BRAF and MEK for the treatment of patients with otherwise refractory BRAF mutant melanoma have demonstrated impressive efficacy, and combination treatment with these agents may prove to be even more effective.
For the rapid and sensitive screening of epidermal growth factor receptor (EGFR) hot-spot mutations, we developed a novel method combining mutant-enriched PCR with amplification refractory mutation system (ARMS) TaqMan real-time PCR in a one-step reaction tube.
ARMS strategy (amplification refractory mutation system) also implies the use of fluorescent dye for the quantitative determination of the mutant allele by real-time PCR.
ACB-PCR: Allele-specific competitive blocker PCR; ARMS: Amplification refractory mutation system; Cq: Quantification cycle; dNTPs: Deoxynucleotide triphosphate; HRM: High resolution melting; MPN: Myeloproliferative neoplasm; MUT: Mutant; NTC: No-template control; PCR: Polymerase chain reaction; WT: Wild-type.
Mutant mitochondrial DNA was not detected in the blood lymphocytes when measured using real-time amplification refractory mutation system quantitative PCR analysis (RT-ARMS qPCR), as previously described [ 2, 10].
Transgenic strains over-expressing a biochemically active but compound-refractory CDPK1 mutant ('G128Q') fail to show reduced susceptibility to the compound in vivo, suggesting that selective inhibition of this enzyme is not responsible for the enhanced anti-parasitic potency of the imidazopyridine analog.
In this study, both full length CTMP, and a CTMP mutant refractory to N-terminal cleavage and leading to an immature protein promote clustering of spherical mitochondria, suggesting a role for CTMP in the fission process.
Furthermore, dominant positive β-catenin mutant refractory to proteasome-mediated degradation rescued the growth inhibitory effect of CXXC4, indicating that CXXC4 might inhibit gastric carcinogenesis through attenuating wnt signaling.
The data presented pave the road toward the rational design of more potent and selective inhibitors of CK2 and the generation of CK2 mutants refractory to inhibition, useful to probe the implication of CK2 in specific cellular functions.
