A cutting edge article entitled “Immunosuppressed Microenvironment – An Emerging Target in Prostate Cancer Management” has been published in the peer-reviewed journal Oncology & Hematology Review, explaining how a detailed understanding of the tumor microenvironment of prostate cancer can lead to insights into the mechanisms leading to hormonal and chemotherapeutic resistance in this type of cancer.
Prostate cancer is the most common malignancy among American and European men, with about 910,000 cases diagnosed every year worldwide. Because the growth and replication of prostate cells is dependent on androgens, the common initial treatment for prostate cancer is hormonal therapy, which although capable of slowing disease progression, can result in hormone-refractory disease, a condition known as metastatic castrate-resistant prostate cancer (mCRPC).
The recent review, written by Joaquim Bellmunt, MD, PhD, Director, Bladder Cancer Center Dana-Farber Cancer Institute, Karim Fizazi MD, PhD, Head of Cancer Medicine Department, Institut Gustave Roussy, Villejuif, France and Geetha Srikrishna, PhD, Research Assistant Professor, Stanford Burnham Medical Research Institute, focuses on the tumor microenvironment and its capacity to promote tumor growth and metastases through the inhibition of the patient’s immune system.
There are multiple cellular and molecular components present in this microenvironment that account for possible therapeutic targets, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), toll-like receptors (TLRs) and the pro-inflammatory protein S100A9, which has been shown in Phase II clinical trials to bind tasquinimod, a drug targeting the tumor microenvironment through modulation of the immune system and inhibition of angiogenesis and metastasis.
Throughout the advances in the field of immunotherapy, biomedical research has discovered several agents that can modulate tumor cell microenvironment, such as sipuleucel T, a therapeutic cancer vaccine for prostate cancer and ipilimumab, a recombinant human monoclonal antibody that binds to CTLA-4 and blocks the interaction with its ligands, enhancing T-cell activation and proliferation. Just recently, two stories concerning anti-CTLA4 monoclonal antibodies were covered by Immuno-Oncology News — the strategic collaboration between Bristol-Meyers Squibb and Ono Pharmaceutical with the objective to develop ipilimumab as a combination therapy with; and the successful combination of entinostat with both anti-PD1 and anti-CTLA4 monoclonal antibodies to treat metastatic cancer in mouse models by Syndax Pharmaceuticals.
The primary site of metastasis in prostate cancer patients is the bone. As such, the bone microenvironment is also seen as a potential therapeutic target. Several clinical studies have focused on this niche, for example, denosumab, a rank-L inhibitor that can prevent bone metastasis, was shown to delay time to first skeletal event, although no with no improvements in overall survival (OS). Moreover, Radium-223, an alpha-emitter with high bone affinity, can delay bone metastasis as well as significantly improving OS.
A better understanding of the complex relationship between prostate cancer and its specific tumor microenvironment can represent a promising opportunity to develop new and improved anti-cancer therapies.