Modulated electro-hyperthermia induced p53 driven apoptosis and cell cycle arrest additively support doxorubicin chemotherapy of colorectal cancer in vitro.
In this review, we have set the spotlight on role of JAK/STAT, TGF/SMAD, Notch, WNT/β-Catenin, SHH/GLI and p53 pathways in the development and progression of colorectal cancer.
SIGNIFICANCE: The TRIM67/p53 axis represents a novel therapeutic target that could be harnessed to improve chemotherapy efficacy in colorectal cancer expressing wild-type p53 but with repressed p53 signaling.
Accordingly, the suppression of the mutant p53 function via the inhibition of nuclear accumulation is expected to be an effective strategy against malignant progression of colorectal cancer.
In conclusion, our findings demonstrate mutant p53 may cause chemo-resistance of tumor because of inactivating PUMA transcription, which prompts some new insights for clinical therapy of cancer patients with mutant p53.<b>Abbreviations:</b> CRC: Colorectal cancer; CDKs: Cyclin-dependent kinases; PUMA: p53 up-regulated modulator of apoptosis; PDGF: the platelet-derived growth factor; WT p53: wild-type p53 protein; mutp53: mutant p53 proteins; BAX: Bcl-2-associated X protein; NOXA: Phorbol-12-myristate-13-acetate-induced protein 1.
APC and TP53 mutations were less frequent in MC compared to those in TCGA-CON (p < 0.001 and 0.003, respectively) whereas KRAS mutation was prevalent (p = 0.041).
An association was also suggested when colorectal cancer was diagnosed 4 to <6 years after p53 measurement (RR = 1.84; 95% CI, 0.89-3.79), but not 6 or more years later (RR = 1.15; 95% CI, 0.44-2.99).<b>Conclusions:</b> If these results are confirmed, serum p53 antibodies may be useful on a panel of early detection markers for colorectal cancer.<b>Impact:</b> Individuals who were seropositive for p53 antibodies were twice as likely to develop colorectal cancer within the next 3 years compared with those who were seronegative.
These data in aggregate suggested that activation of p53 was required for costunolide inhibition of GLS1 resulting in blockade of glutaminolysis and inhibition of proliferation in colorectal cancer cells, which was a novel mechanism underlying the antitumor activity of costunolide against colorectal cancer.