CHALLENGES IN MANIPULATING IMMUNE SYSTEM TO TREAT PROSTATE CANCER/IZAZOVI MANIPULIRANJA IMUNOLOSKIM SUSTAVOM U SVRHU LIJECENJA RAKA PROSTATE

First cancer vaccine that was approved for routine therapy was sipuleucel-T for treatment of patients with metastatic castration resistant prostate cancer. However, other immunotherapy drugs evaluated in prostate cancer, particularly immune checkpoint inhibitors, have failed to show therapeutic effe...

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Bibliographic Details
Published in:Acta clinica Croatica (Tisak) 2019-11, Vol.58 (S2), p.76
Main Authors: Samija, Ivan, Frobe, Ana
Format: Article
Language:English
Subjects:
Abiraterone
Antineoplastic agents
Cancer metastasis
Cancer treatment
Cancer vaccines
Care and treatment
Enzalutamide
Genetic aspects
Health aspects
Immune system
Immunotherapy
Ipilimumab
Pembrolizumab
Prostate cancer
Tumors
Vaccines
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Summary:First cancer vaccine that was approved for routine therapy was sipuleucel-T for treatment of patients with metastatic castration resistant prostate cancer. However, other immunotherapy drugs evaluated in prostate cancer, particularly immune checkpoint inhibitors, have failed to show therapeutic effect. There are several potential explanations for lack of response of prostate cancer to these drugs. These explanations, which are related to specific genetic (e.g. low mutational burden) and immunological (e.g. immunosuppressive tumor immune microenvironment) background of prostate cancer are discussed in this review. Also, new therapeutic strategies to overcome prostate cancer immunotherapy resistance and to select subgroups of patients that could benefit from immunotherapy are outlined. Key words: Prostate Cancer; Immunotherapy; Cancer Vaccines; Immune Checkpoint Inhibitors; Tumor Immune Evasion Sažetak Prva vakcina za rak koja je odobrena za rutinsko lijecenje bio je sipuleucel-T za lijecenje bolesnika s metastatskim kastracijski rezistentnim rakom prostate. Medutim, drugi imunoterapijski lijekovi koji su bili istraživani u bolesnika s rakom prostate, posebno inhibitori imunološke kontrolne tocke, nisu pokazali terapijski ucinak. Nekoliko je mogucih objašnjenja za nedostatak terapijskog odgovora na ove lijekove kod raka prostate. Ta objašnjenja koja su vezana uz specificna geneticka (npr. nisko mutacijsko opterecenje) i imunološka (npr. imunosupresivni tumorski imunološki mikrookoliš) obilježja raka prostate opisana su u ovom preglednom radu. Takoder, prikazane su nove terapijske strategije s ciljem prevladavanja otpornosti raka prostate na imunoterapiju i za odabir podskupina bolesnika u kojih se može ocekivati korist od imunoterapije. Kljucne rijeci: rak prostate; imunoterapija; vakcine za rak; inhibitori imunološke kontrolne tocke; izmicanje tumora imunološkom nadzoru
ISSN:0353-9466
DOI:10.20471/acc.2019.58.s2.13