Targeting Prostate Cancer, the 'Tousled Way'.
Siddhant BhoirArrigo De BenedettiPublished in: International journal of molecular sciences (2023)
Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer (PCa) treatment, with success in developing more effective inhibitors of androgen synthesis and antiandrogens in clinical practice. However, hormone deprivation and AR ablation have caused an increase in ADT-insensitive PCas associated with a poor prognosis. Resistance to ADT arises through various mechanisms, and most castration-resistant PCas still rely on the androgen axis, while others become truly androgen receptor (AR)-independent. Our research identified the human tousled-like kinase 1 (TLK1) as a crucial early mediator of PCa cell adaptation to ADT, promoting androgen-independent growth, inhibiting apoptosis, and facilitating cell motility and metastasis. Although explicit, the growing role of TLK1 biology in PCa has remained underrepresented and elusive. In this review, we aim to highlight the diverse functions of TLK1 in PCa, shed light on the molecular mechanisms underlying the transition from androgen-sensitive (AS) to an androgen-insensitive (AI) disease mediated by TLK1, and explore potential strategies to counteract this process. Targeting TLK1 and its associated signaling could prevent PCa progression to the incurable metastatic castration-resistant PCa (mCRPC) stage and provide a promising approach to treating PCa.
Keyphrases
- prostate cancer
- poor prognosis
- radical prostatectomy
- single cell
- long non coding rna
- cell therapy
- clinical practice
- endothelial cells
- oxidative stress
- squamous cell carcinoma
- cancer therapy
- cell death
- stem cells
- endoplasmic reticulum stress
- signaling pathway
- artificial intelligence
- machine learning
- drug delivery
- biofilm formation
- climate change
- replacement therapy
- radiofrequency ablation
- pluripotent stem cells