The long and winding road for the development of tasquinimod as an oral second-generation quinoline-3-carboxamide antiangiogenic drug for the treatment of prostate cancer

Abstract

Importance of the field: Prostate cancer is the mostly commonly diagnosed non-skin cancer in males. The culmination of the last 70 years of clinical drug development has documented that androgen ablation plus taxane-based systemic chemotherapy enhances survival, but is not curative, in metastatic prostate cancer. To effect curative therapy, additional drugs must be developed that enhance the response when combined with androgen ablation/taxane therapy.

Areas covered in this review: The history of the discovery and development of tasquinimod as a second-generation oral quinoline-3-carboxamide analogue for prostate cancer will be presented.

What the reader will gain: The mechanism for such anticancer efficacy is via tasquinimod's ability to inhibit the 'angiogenic switch' within cancer sites required for their continuous lethal growth.

Take home message: Tasquinimod is a novel inhibitor of tumor angiogenesis that enhances the therapeutic anticancer response when combined with other standard-of-care modalities (radiation, androgen ablation, and/or taxane-based chemotherapies) in experimental animal models, but does not inhibit normal wound healing. It has successfully completed clinical Phase II testing in humans and will shortly enter registration Phase III evaluation for the treatment of metastatic prostate cancer.

Figure 1

Chemical structure of piroxicam [CAS number 36322-90-4; (8E)-8-[hydroxy-(pyridin-2-ylamino)methylidene]-9-methyl-10,10-dioxo-10λ6-thia-9-azabicyclo[4.4.0] deca-1,3,5-trien-7-one].

Figure 2

Chemical structure of roquinimex [LS-2616; CAS number 84088-42-6; 4-hydroxy-N, 1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide].

Figure 3

Chemical structure of laquinimod [ABR-215062; CAS number 248282-07-7; N-ethyl-N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-3-quinoline-carboxamide].