The Underestimated Role of the p53 Pathway in Renal Cancer

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 carci‐ noma (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 al‐ tered p53 in RCC is mandatory for improving early diagnosis, evaluating the prognosis and de‐ veloping novel potential therapeutic targets for better RCC treatment.