The TP53 gene is one of the most common genes seen in breast cancer tumor cells which codes for the P53 protein. For years scientists have known about the frequency of P53 seen in breast cancer cells, but only recently have they begun to explore the role of mutations in this protein and how they affect the overall effectiveness of chemotherapy.
The first paper I read was written in 1998 and it studied 40 tumors; 29 of which were linked to BRCA1 and 11 of which were linked to BRCA2. The scientists examined the tumors for mutations in various genes linked to breast cancer development, one of which being the TP53 gene. One of the most staggering statistics gathered from this study was the fact that P53 mutations were seen in 80% of the tumors, affecting 83% of BRCA1-linked tumors and 73% of BRCA2-linked tumors. Mutations of P53 most commonly resulted in the upregulation of the protein which was most likely the result of a change in the cell cycle checkpoints. The paper concluded that even though P53 may not be mutated in every case, different components of the P53-dependent cell cycle could have been altered which may have a direct effect on the tumors.
The second paper I read was written by French scientists in 2013, and the study was prompted because the scientists realized that even though previous findings showed an obvious central role of P53 in cancer, the status of TP53 has never been studied as a way to manage breast cancer. Mutations of the TP53 gene are the most common across all breast cancer sub-types, seen in 30% of tumors. In breast cancer patients, tumors are determined to be ER(+) or ER(-), meaning they are either receptive (+) or nonreceptive (-) to estrogen. The paper suggested that having a tumor that is ER(-) with TP53 mutations is the best case scenario for patients, because the accumulation of genetic mutations and abnormalities in these tumors lead to a better response to chemotherapy compared to ER(+) TP53 wild type tumors.
After reading these two articles, it is clear that there is much more research needed in this field for any hope of finding a way to completely eliminate these tumors. The largest challenge when treating breast cancers is the fact that there are so many types of tumors which can range in their response to chemotherapy. I believe these studies are huge leaps forward for the field of oncology, but more studies need to be conducted on P53 as well as any other genes thought to play a role in any stage of tumorigenesis. I think for now studies should focus on P53 due to its widespread activity in breast cancer because it may hold the secrets to the main pathways that allow for tumor growth. If we can find even one pathway responsible for tumor growth, we may be able to break the pathway and cure cancers that were difficult to near impossible to treat before.
Links to articles:
Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers:
p53 in breast cancer subtypes and new insights into response to chemotherapy: