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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The Underestimated Role of the p53 Pathway in Renal Cancer
Alessandra Amendolare1,2, Flaviana Marzano2, Vittoria Petruzzella3
1Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70121 Bari, Italy.
Abstract:
The TP53 tumor suppressor gene is known as the guardian of the genome, playing a pivotal role in controlling genome integrity, and its functions are lost in more than 50% of human tumors due to somatic mutations. This percentage rises to 90% if mutations and alterations in the genes that code for regulators of p53 stability and activity are taken into account. Renal cell carcinoma (RCC) is a clear example of cancer that despite having a wild-type p53 shows poor prognosis because of the high rate of resistance to radiotherapy or chemotherapy, which leads to recurrence, metastasis and death. Remarkably, the fact that p53 is poorly mutated does not mean that it is functionally active, and increasing experimental evidences have demonstrated this. Therefore, RCC represents an extraordinary example of the importance of p53 pathway alterations in therapy resistance. The search for novel molecular biomarkers involved in the pathways that regulate altered p53 in RCC is mandatory for improving early diagnosis, evaluating the prognosis and developing novel potential therapeutic targets for better RCC treatment.
Insights
The TP53 tumor suppressor gene, crucial for genome integrity, is often functionally altered in renal cell carcinoma (RCC), leading to therapy resistance. Identifying biomarkers for altered p53 pathways is vital for improved RCC diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The TP53 tumor suppressor gene, or "guardian of the genome," is critical for maintaining genomic stability.
- Somatic mutations in TP53 occur in over 50% of human cancers, with alterations in its regulators affecting up to 90%.
- Renal cell carcinoma (RCC) frequently exhibits wild-type TP53 but shows resistance to therapies, indicating functional p53 pathway alterations.
Purpose of the Study:
- To highlight the significance of p53 pathway alterations in therapy resistance in RCC.
- To emphasize the need for novel molecular biomarkers in RCC.
- To underscore the importance of understanding p53 pathway dysregulation for improved diagnosis and therapeutic strategies.
Main Methods:
- Review of existing literature on TP53 gene mutations and alterations.
- Analysis of experimental evidence demonstrating functional p53 inactivation despite wild-type status in RCC.
- Focus on the role of p53 pathway regulators in RCC prognosis and treatment resistance.
Main Results:
- TP53 mutations and alterations in its regulators are prevalent in human cancers, impacting genome integrity.
- RCC serves as a model where wild-type p53 does not guarantee functional activity, correlating with poor therapeutic outcomes.
- Functional inactivation of the p53 pathway is a key driver of resistance to radiotherapy and chemotherapy in RCC.
Conclusions:
- Altered p53 pathway function, not just mutation, is critical in RCC and contributes to poor prognosis.
- Identifying novel biomarkers within the p53 pathway is essential for advancing early diagnosis and treatment of RCC.
- Targeting the dysregulated p53 pathway holds potential for developing new therapeutic strategies for renal cell carcinoma.
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