Immunotherapy as a Precision Medicine Tool for the Treatment of Prostate Cancer

Abstract

Prostate cancer (PCa) is the most frequently diagnosed type of cancer among Caucasian males over the age of 60 and is characterized by remarkable heterogeneity and clinical behavior, ranging from decades of indolence to highly lethal disease. Despite the significant progress in PCa systemic therapy, therapeutic response is usually transient, and invasive disease is associated with high mortality rates. Immunotherapy has emerged as an efficacious and non-toxic treatment alternative that perfectly fits the rationale of precision medicine, as it aims to treat patients on the basis of patient-specific, immune-targeted molecular traits, so as to achieve the maximum clinical benefit. Antibodies acting as immune checkpoint inhibitors and vaccines entailing tumor-specific antigens seem to be the most promising immunotherapeutic strategies in offering a significant survival advantage. Even though patients with localized disease and favorable prognostic characteristics seem to be the ones that markedly benefit from such interventions, there is substantial evidence to suggest that the survival benefit may also be extended to patients with more advanced disease. The identification of biomarkers that can be immunologically targeted in patients with disease progression is potentially amenable in this process and in achieving significant advances in the decision for precision treatment of PCa.

Pharmacometabolomics Applied to Personalized Medicine in Urological Cancers

“…Despite the benefits, several adverse effects have been associated with ADT including sexual side effects (e.g., loss of libido, erectile dysfunction, among others), osteoporosis, anemia, fatigue, depression, and cardiovascular complications [ 31 ]. Moreover, after an initial response to ADT, some patients develop castration-resistant PCa (CRPCa), a progression of the disease [ 32 ]. Novel anti-androgen drugs such as bicalutamide, nilutamide, or enzalutamide have been developed to treat this condition but the prognosis of CRPCa remains poor [ 25 , 32 ].…”

“…Moreover, after an initial response to ADT, some patients develop castration-resistant PCa (CRPCa), a progression of the disease [ 32 ]. Novel anti-androgen drugs such as bicalutamide, nilutamide, or enzalutamide have been developed to treat this condition but the prognosis of CRPCa remains poor [ 25 , 32 ]. In these cases, ADT is commonly recommended for symptom control or prescribed in combination with chemotherapy (e.g., docetaxel, cabazitaxel, mitoxantrone) to slow the progression of advanced PCa [ 28 , 30 ].…”

“…The use of diagnostic biomarkers, such as the serum prostate-specific antigen (PSA), which is commonly used for PCa screening, prostatic acid phosphate (PAP), and prostate-specific membrane antigen (PSMA), as target antigens in immunotherapy has been investigated [ 32 , 35 ]. Moreover, the scientific community has been interested in combining immunotherapy and targeted therapy to increase the sensitivity of cancer cells to antitumor effects of antineoplastic drugs [ 36 ].…”

Immunotherapy in treatment of metastatic prostate cancer: An approach to circumvent immunosuppressive tumor microenvironment

“…Recent advancements in knowledge of tumor immune microenvironment have led to the development of several strategies for eradicating prostate cancer cells through immune system activity. There have been promising immunotherapies developed through activating the innate and adaptive immune response, such as cancer vaccines and adoptive cell therapy, or inhibiting immune‐suppressive elements, such as immune checkpoint inhibitors and antibodies 53 . A cell‐based vaccine Sipuleucel‐T has been approved by FDA for the treatment of asymptomatic or minimally symptomatic metastatic CRPC in April, 2010.…”

Prostate Cancer—Focus on Cholesterol

“…Prostate cancer (PC) with high incidence (>1.1 million new cases each year) and mortality (~300,000 deaths per year) presents a significant global public health burden [ 1 , 2 ]. Established risk factors of PC are age, race and family history of disease [ 3 , 4 ]. Although, many risk factors are non-modifiable, association with preventable high fat diets, risk of PC and progression of the disease have been observed in different studies [ 5 , 6 , 7 , 8 , 9 ].…”