Resistance to prostate cancer treatments

Abstract

A review of the current treatment options for prostate cancer and the formation of resistance to these regimens has been compiled including primary, acquired, and cross-resistance. The diversification of the pathways involved and the escape routes the tumor is utilizing have been addressed. Whereas early stages of tumor can be cured, there is no treatment available after a point of no return has been reached, leaving palliative treatment as the only option. The major reasons for this outcome are the heterogeneity of tumors, both inter-and intra-individually and the nearly endless number of escape routes, which the tumor can select to overcome the effects of treatment. This means that more focus should be applied to the individualization of both diagnosis and therapy of prostate cancer. In addition to current treatment options, novel drugs and ongoing clinical trials have been addressed in this review.

Glucocorticoid Receptor and β-Catenin Interact in Prostate Cancer Cells and Their Co-Inhibition Attenuates Tumorsphere Formation, Stemness, and Docetaxel Resistance

“…However, while the role of GR signaling in promoting chemoresistance has been suggested for other solid tumors [ 60 , 61 , 62 ], its role in mCRPC chemoresistance just recently emerged [ 16 , 22 , 27 ]. The dual role of GR signaling in promoting resistance to both ARSI and taxane chemotherapy during the treatment of mCRPC implicates this nuclear receptor as a key player in PCa therapy cross-resistance, a common occurrence in which a pre-existing or acquired mechanism that promotes resistance to a particular drug treatment (e.g., ARSI) results in resistance to a subsequent drug or therapy (e.g., taxane chemotherapy) [ 6 , 63 ]. Therapy cross-resistance has implications for determining the safest and more effective sequence in which different drugs should be administered during PCa progression [ 6 ].…”

Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer

“…PCa is one of the most common tumors in men. Due to its heterogeneity and progressive nature, it remains incurable ( 41 ). Valid prognostic models based on specific biomarkers can accurately predict survival outcomes for the effective management of PCa patients ( 42 ).…”

Synergizing Proteolysis-Targeting Chimeras and Nanoscale Exosome-Based Delivery Mechanisms for HIV and Antiviral Therapeutics

“…ARV-471, which targets the estrogen receptor, is currently in a Phase II clinical trial for patients with ER+/HER2- locally advanced or metastatic breast cancer . Early results have shown that ARV-471 has a manageable safety profile and displays clinical activity, lending further support to the clinical potential of PROTACs.…”

“…Notable among these are ARV-110 and ARV-471, both in trials for cancer treatment. ARV-110, designed to degrade the androgen receptor, is being tested in a Phase II clinical trial for metastatic castration-resistant prostate cancer . Preliminary results from the trial indicate that ARV-110 is generally well-tolerated and demonstrates potential antitumor activity, signifying a major step toward realizing the promise of PROTACs for human treatment.…”

“…This amalgamation seeks to surmount the remaining challenges associated with PROTACs, including bioavailability and off-target effects. Employing exosomes as delivery vectors for PROTACs enhances the bioavailability and target specificity of these molecules, potentially maximizing their therapeutic efficacy. − In the current landscape of targeted therapy, PROTACs hold a prominent position, representing a dynamic area of research with the potential to radically transform treatment modalities for a host of diseases.…”