Targeted Therapy for Androgen Receptor Signaling Inhibitors (ARSI)-Resistant Prostate Cancer

Dear Colleagues,

Androgen deprivation therapy (ADT) is the first-line systemic treatment for advanced prostate cancer. Nevertheless, these tumors inevitably adapt to ADT by maintaining sustained androgen receptor (AR) signaling via several back-door mechanisms, resulting in highly aggressive castration-resistant prostate cancer (CRPC). Although next-generation AR-signaling inhibitors (ARSI), such as abiraterone, apalutamide, and enzalutamide intensively inhibit AR signaling, the median survival rates following diagnosis remain dismal. This is due to tumor adaptation against ARSI, which has driven the emergence of several new variants of extremely aggressive and lethal prostate tumors, including neuroendocrine PCa (NEPC), AR-low prostate cancer (ARLPC), double-negative CRPC (AR-null and NE-null aka DNPC), amphicrine prostate cancer (both AR- and NE-positive AMPC) and stem-cell-like castration-resistant prostate cancer (SCL-CRPC). Therefore, unraveling the underlying mechanisms to identify potential therapeutic interventions to treat these lethal tumors has become a critical challenge in the post-ARSI era. It is equally important to uncover the different molecular characteristics of these fatal cancers, which can then be used as diagnostic and prognostic biomarkers to enable tailored treatments for patients.

We are pleased to invite you to submit original research, commentaries, or review articles that describe the molecular mechanisms of these newly emerging ARSI-resistant PCa. Your article should focus on the therapeutics, diagnostics, biomarker, or mechanistic studies unraveling the transitional mechanisms from CRPC to ARSI-resistant lethal cancers.

This Special Issue aims to gather novel basic and translational data, as well as perspectives particularly focused on NEPC, ARLPC, DNPC, AMPC and SCL-CRPC.

Research areas may include (but are not limited to) the following:

• The discovery of the molecular mechanisms and drivers of ARSI-resistant PCa (including transcriptional, epigenetic and post-translational controls).
• Identification and validation of druggable therapeutic targets for ARSI-resistant PCa.
• Identification of novel prognostic and predictive biomarkers of ARSI resistance to enable patient stratification and tailor treatment.
• Cell lines, PDX and mouse models for NEPC, DNPC, AMPC and SCL-PC.
• Effective strategies for targeting tumor microenvironment.
• The discovery of novel drugs either alone or in combination. Repurposing of FDA-approved drugs with or without chemotherapy-sensitizing agents to overcome chemo and drug resistance in ARSI-resistant cancer patients.

I look forward to receiving your contributions.

Dr. Kavita Shah
Guest Editor

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• androgen receptor signaling inhibitors (ARSI)-resistant prostate cancer
• neuroendocrine prostate cancer (NEPC)
• AR-low prostate cancer (ARLPC)
• double-negative prostate cancer (DNPC)
• amphicrine prostate cancer (AMPC)
• drug discovery
• druggable therapeutic target
• biomarkers
• PDX models