Targeting Prostate Cancer, The ‘Tousled Way’

Siddhant Bhoir; Arrigo De benedetti

doi:10.20944/preprints202306.1180.v3

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preprints.org > biology and life sciences > biochemistry and molecular biology > doi: 10.20944/preprints202306.1180.v3

Preprint Review Version 3 Preserved in Portico This version is not peer-reviewed

Targeting Prostate Cancer, The ‘Tousled Way’

Siddhant Bhoir

and

Arrigo De benedetti

Version 1 : Received: 13 June 2023 / Approved: 16 June 2023 / Online: 16 June 2023 (07:09:22 CEST)
Version 2 : Received: 20 June 2023 / Approved: 21 June 2023 / Online: 21 June 2023 (08:07:56 CEST)
Version 3 : Received: 21 June 2023 / Approved: 25 June 2023 / Online: 25 June 2023 (03:56:10 CEST)

A peer-reviewed article of this Preprint also exists.

Bhoir, S.; De Benedetti, A. Targeting Prostate Cancer, the ‘Tousled Way’. Int. J. Mol. Sci. 2023, 24, 11100. Bhoir, S.; De Benedetti, A. Targeting Prostate Cancer, the ‘Tousled Way’. Int. J. Mol. Sci. 2023, 24, 11100.

Abstract

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 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 under-represented 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.

Keywords

PCa; AR; ADT; TLK1 signaling; pathway inhibition

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1

Received: 25 June 2023
Commenter: arrigo de benedetti
Commenter's Conflict of Interests: Author

Comment: Now the graphical Abstract is missing. I am not sure how it could have happened since the doc file included it. I am uploading it again (vs 3). Although we are resubmitting it, there are no changes to the previous version.

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