In chapter 14, we talked about tumor-supressor genes. A tumor-supressor gene is a gene that, under normal conditions, encodes a protein that prevents cancer. However, when a mutation eliminates its function, cancer may occur aka cancer-causing mutations in tumor-suppressor genes are due to a loss of activity. One tumor-supressor gene that we have talked about is p53. p53 is a transcription factor that acts as a sensor of DNA damage. It promotes DNA repair, prevents the progression through the cell cycle, and promotes apoptosis. It is present in the G1 phase of the cell cycle and controls the first checkpoint. About 50% of all human cancers are associated with mutations in this gene. This includes malignant tumors of the lung, breast, esophagus, liver, bladder, and brain, as well as leukemias and lymphomas.
This article talks about p53 and its molecular basis to chemoresistance in breast cancer. As you may have known, TP53 is the gene that encodes the tumor protein p53. Mutations in this gene have been known to be linked with resistance to anthracyclines (class of drugs used in cancer chemotherapy) and mitomycin (anticancer drug that belongs to the family of drugs called antitumor antibiotics) in breast cancer. This article goes over the possible responsibilities of different parts in the p53 cascade giving respect to drug resistance. The full article goes over the research that took place. It also talks about p53 activation in response to genotoxic stress and phsphorylations by ataxia telangiectasia mutated/ataxia telangiectasia and radiation resistance gene 3 related (ATM/ATR). Chk1 and 2 are also considered to be very important. A little while back researchers discovered that nonsense mutations in CHEK2 that encoded the chk2 protein, were found to predict resistance to anthracycline therapy in some tumors that contained wild-type TP53. As of right now, there is no evidence that MDM2 amplifications in breast cancers are resistant to anthracyclines. The roles of p53 isoforms and p53-induced transcription of non-coding RNA are yet to be determined. Experts say that disturbances affecting the p53 pathways may play key roles in chemoresistance in cancer. Although TP53 is not an exact marker for drug resistance, it still may be considered a signal for identifying critical gene cascades.
This is a simple diagram that shows the pathway of p53.
This article talks about p53 and its molecular basis to chemoresistance in breast cancer. As you may have known, TP53 is the gene that encodes the tumor protein p53. Mutations in this gene have been known to be linked with resistance to anthracyclines (class of drugs used in cancer chemotherapy) and mitomycin (anticancer drug that belongs to the family of drugs called antitumor antibiotics) in breast cancer. This article goes over the possible responsibilities of different parts in the p53 cascade giving respect to drug resistance. The full article goes over the research that took place. It also talks about p53 activation in response to genotoxic stress and phsphorylations by ataxia telangiectasia mutated/ataxia telangiectasia and radiation resistance gene 3 related (ATM/ATR). Chk1 and 2 are also considered to be very important. A little while back researchers discovered that nonsense mutations in CHEK2 that encoded the chk2 protein, were found to predict resistance to anthracycline therapy in some tumors that contained wild-type TP53. As of right now, there is no evidence that MDM2 amplifications in breast cancers are resistant to anthracyclines. The roles of p53 isoforms and p53-induced transcription of non-coding RNA are yet to be determined. Experts say that disturbances affecting the p53 pathways may play key roles in chemoresistance in cancer. Although TP53 is not an exact marker for drug resistance, it still may be considered a signal for identifying critical gene cascades.
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