Abstract
Simple SummaryThere is still no effective treatment for advanced prostate cancer. CAR-T therapy is a promising approach; however, many obstacles remain for the treatment of solid tumors due to the complex physical barriers and inhibitory microenvironment in solid tumors. Single CAR-T therapy has a low response rate and a high recurrence rate. With the enhancement of CAR-T itself and the gradual improvement of the immune microenvironment, the number of CAR-T weapons against tumors is increasing. This article discusses the current status and future of CAR-T therapy for prostate cancer. We believe that the enhancement and modification of CAR-T or CAR-T combined with other therapies are expected to be a breakthrough in the treatment of prostate cancer.The incidence rate of prostate cancer is higher in male cancers. With a hidden initiation of disease and long duration, prostate cancer seriously affects men’s physical and mental health. Prostate cancer is initially androgen-dependent, and endocrine therapy can achieve good results. However, after 18–24 months of endocrine therapy, most patients eventually develop castration-resistant prostate cancer (CRPC), which becomes metastatic castration resistant prostate cancer (mCRPC) that is difficult to treat. Chimeric Antigen Receptor T cell (CAR-T) therapy is an emerging immune cell therapy that brings hope to cancer patients. CAR-T has shown considerable advantages in the treatment of hematologic tumors. However, there are still obstacles to CAR-T treatment of solid tumors because the physical barrier and the tumor microenvironment inhibit the function of CAR-T cells. In this article, we review the progress of CAR-T therapy in the treatment of prostate cancer and discuss the prospects and challenges of armed CAR-T and combined treatment strategies. At present, there are still many obstacles in the treatment of prostate cancer with CAR-T, but when these obstacles are solved, CAR-T cells can become a favorable weapon for the treatment of prostate cancer.
Highlights
According to the 2020 Global Cancer Statistics Report, the incidence rate of prostate cancer ranks second in all male malignant tumors [1]
Androgen deprivation therapy (ADT) combined with chemotherapy or endocrine therapy, such as abiraterone and enzalutamide, are still the schemes recommended by some guidelines
Endocrine therapy is still the basis of prostate cancer treatment, but when the hormone sensitive prostate cancer develops into castration resistant prostate cancer, the effect of treatment significantly decreases, and the mortality increases
Summary
According to the 2020 Global Cancer Statistics Report, the incidence rate of prostate cancer ranks second in all male malignant tumors [1]. When the disease progresses to castration resistant prostate cancer (CRPC), ADT-based treatment is not so easy. The application of chemotherapeutic drugs leads to different degrees of drug resistance and many side effects [6] Other therapies such as RA233, PARP inhibitors and targeted radioactive ligands have certain curative effects, they cannot fundamentally solve the problem of poor prognosis of patients with CRPC. Immune checkpoint inhibition and CAR-T cell therapy are new methods of tumor immunotherapy in recent years, which have achieved remarkable results in the treatment of many tumors. The combination therapy of CAR-T cells and the way of blocking immune checkpoints are potential ways to overcome the obstacles of existing effective treatment. We review studies of CAR-T cells in the treatment of prostate cancer, and discuss the prospects for prostate cancer treatment by armed CAR-T and combined therapy
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