"Evaluation of CDK4 as a Biomarker in Prostatic Neoplasms: Expression, Molecular Role, and Diagnostic Potential"

• Grant number: 25/11483-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Carlos Eduardo Fonseca Alves
• Grantee: Ana Giulia Gabriel da Rocha Cesario
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Prostate cancer (PC) is the second most common type of neoplasm in humans and one of the leading causes of mortality. Although its prevalence in dogs is relatively low (estimated between 2% and 12%), prostate cancer in this species is highly aggressive and exhibits high metastatic rates. The dog is the only mammal, besides humans, that spontaneously develops this neoplasm. Similar to humans, dogs frequently develop osteoblastic bone metastases, especially in the pelvis and lumbar spine, often accompanied by neurological signs. Due to these features and the morphological, physiological, and histological similarities, the dog is considered a relevant translational model for studying human prostate cancer, particularly for the investigation of new biomarkers and therapeutic approaches. Cyclin-dependent kinases (CDKs) play a central role in cell cycle regulation. Specifically, CDK4 and CDK6, in association with cyclin D, control the progression from the G1 to the S phase. This pathway is deregulated in various types of human tumors, including advanced and metastatic prostate cancer, in which amplifications of the CDK4 and CDK6 genes have been described. Therefore, our objective is to investigate the protein expression and the presence of mutations in the CDK4 gene (via PCR) in tissues from dogs diagnosed with prostatic carcinoma. CDK4 protein expression will be evaluated using immunohistochemistry, and CDK4 gene mutations will be analyzed using the PCR technique. This project may clarify the involvement of the CDK4-cyclin D-INK4-Rb pathway in canine prostate cancer, contributing to a better understanding of the molecular mechanisms that regulate cell proliferation in this tumor type. Demonstrating CDK4 overexpression could support its application as a diagnostic, prognostic, or therapeutic biomarker, expanding the clinical management options for the disease in dogs. (AU)