Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer

Abstract

Castrate-resistant prostate cancer (CRPC) is a disease where survival is poor and treatment is challenging. Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC. However, despite the presence of new approved drugs such as enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and alpharadin, there is still an unmet need for novel agents with different mechanisms of action to target CRPC. Based on earlier studies demonstrating therapeutic potential of a quinoline-3-carboxamide agent roquinimex as an anticancer drug, efforts were directed to identify other useful members in this class. Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC. The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease. Tasquinimod is an orally available agent that has shown efficacy and favorable safety profile as deduced by the results of Phase I and II clinical trials of this drug in prostate cancer. The place of tasquinimod in the treatment of CRPC patients is currently under examination in an ongoing Phase III clinical trial. In this review, we will discuss tasquinimod, starting from its discovery and current knowledge on potential mechanisms of action to its clinical potential in CRPC.

Pharmacotherapeutic Management of Metastatic, Castration-Resistant Prostate Cancer in the Elderly: Focus on Non-Chemotherapy Agents

“…Tasquinimod is an oral agent that inhibits blood vessel formation, but the mechanism of action is incompletely understood [35]. There are not currently any approved therapies in prostate cancer that interfere with angiogenesis, and there have been multiple negative studies with angiogenesis inhibitors tried in prostate cancer [36–38].…”

Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund’s Adjuvant

“…The first development of quinoline-3-carboxamide analogues was in 1980, when Active Biotech in Sweden identified roquinimex, which later became famous by the trade name, Linomide [ 30 ]. Thereafter, compounds within this class exhibited potent disease-inhibitory effects in experimental models of autoimmune diseases including type II collagen arthritis model in mice [ 31 ], diabetic mice [ 32 ], autoimmune pathologies of the central and peripheral nervous systems [ 33 ], and experimental autoimmune encephalomyelitis [ 34 ].…”

Application of Anti-Inflammatory Agents in Prostate Cancer

“…Tasquinimod (ABR-215050), an oral immunomodulatory compound, reportedly affects the accumulation and function of tumor-suppressive myeloid cells, MDSCs, and M2-like TAMs via targeting the inflammatory protein S100A9 [ 283 , 284 , 285 ]. In a randomized phase 3 trial (NCT01234311), chemotherapy-naive men with metastatic CRPC ( n = 1245) were randomly assigned either tasquinimod or placebo.…”