Abstract
The initial stage of prostatic adenocarcinoma (PaC) has been treated with surgery and radiation therapy, but the advanced stages need systemic novel treatment. Since 2010, several advanced therapeutic innovations have been introduced in various randomized clinical trials to improve survival and reduce morbidity and mortality. Several of these therapeutics have shown substantial survival assistance globally, even in the advanced stages of metastatic castration-resistant prostatic adenocarcinoma (mCRPC). This article describes advanced PaC therapy regimens including chemotherapeutic options, hormonal therapies (abiraterone, enzalutamide), immunotherapeutic agents, and bone-modifying agents. We discussed various pros and cons of gene therapy approaches including Crispr/Cas9 mediation, oncolytic viruses, suicidal genes, and micro-RNA based antitumor therapy. The mCRPC microenvironment is characterized by elevated prostate-specific antigen (PSA) levels, which ultimately trigger the androgen receptor (AR) and its dependent signaling pathways. The advanced therapeutics target these receptors and inhibit the steroidogenic enzymes that play an important role in increasing testosterone (T) and dihydrotestosterone (DHT) levels in the body. These advanced therapeutic novelties also target AR-independent oncogenic signaling pathways by focusing on DNA damage repair (DDR) pathways and their mechanisms. Some of these options appear to be very attractive strategies for acute and chronic stages of PaC and mCRPC treatment by overcoming the mechanisms of resistance.
Highlights
prostatic adenocarcinoma (PaC) is a male-specific cancer of the prostate gland, which serves as the leading cause worldwide associated with interrupted urine flow, urge to urinate frequently at night, blood in the urine and seminal fluid, erectile dysfunction, and enlarged prostate in men
Metastatic castration-resistant prostate cancer (CRPC) is defined by consecutive rises in serum prostatespecific antigen (PSA) levels or/and progression of metastatic spread in the setting of castrate levels of testosterone due to the stage of cancer when it no longer completely responds to treatments that lower testosterone (Vlachostgrios et al, 2017)
Men diagnosed with metastatic castration-resistant prostatic adenocarcinoma (mCRPC) along with increased androgen levels have been treated with androgen deprivation therapeutics, but castration resistance has been observed in all patients which were subsided by advanced therapy that could include additional androgen receptor (AR) axis targeted moieties such as abiraterone and enzalutamide chemotherapy (Litwin and Tan, 2017)
Summary
PaC is a male-specific cancer of the prostate gland, which serves as the leading cause worldwide associated with interrupted urine flow, urge to urinate frequently at night, blood in the urine and seminal fluid, erectile dysfunction, and enlarged prostate in men. 70–80% of patients with PaC develop bone metastases and regional lymph node metastasis is observed in 5–12% of patients (Maolake et al, 2018). If the disease is significantly mitigated by ADT, it is considered as Castration Sensitive Prostate Cancer and accounts for 3% of all PaC. Metastatic castration-resistant prostate cancer (CRPC) is defined by consecutive rises in serum prostatespecific antigen (PSA) levels or/and progression of metastatic spread in the setting of castrate levels of testosterone due to the stage of cancer when it no longer completely responds to treatments that lower testosterone (Vlachostgrios et al, 2017).
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