The role of the p16INK4a gene in the pathogenesis of malignant neoplasms of the bladder

Urothelial carcinoma of the bladder remains a serious medical problem. It is characterized by a diverse clinical course and a high rate of recurrence. The early form, "carcinoma in situ" (PTIs), is rare, accounting for only 2-5% of cases, but it tends to progress. Superficial forms (pT1a and pT1b) account for most newly diagnosed cases (about 70%), but are characterized by a high relapse rate (up to 70%). Approximately one-third of recurrent tumors progress further with the development of metastases. The most severe prognoses are observed in muscle-invasive forms (pT2 and higher), which account for more than a quarter of primary diagnoses. One of the key molecular mechanisms underlying the development of cancer involves alterations to the p16INK4a (CDKN2A) gene, which acts as a tumour suppressor. Under normal conditions, the p16 protein inhibits the cell cycle by suppressing the activity of the CDK4/6-cyclin D1 complex, thereby preventing excessive cell proliferation. Disruption to the function of p16INK4a results in a loss of control over cell division and triggers malignant transformation. Modern treatment approaches include comprehensive measures such as surgery, chemotherapy and radiation therapy, as well as the introduction of personalised medicine based on the molecular profiling of tumours. Further scientific research should focus on developing effective methods of early diagnosis, identifying new biomarkers, and creating individual therapeutic strategies aimed at improving quality of life and increasing life expectancy for cancer patients.