Toll-like receptors as therapeutic targets for cancer

•Overview of the roles of Toll-like receptors in the innate immune system.•Current Toll-like receptor agonists in clinical oncology.•Various Toll-like receptors are in development for cancer therapy.•Focus on Toll-like receptor 7 as a promising potent cancer target.

Stimulation of Toll-like receptors (TLRs) to activate the innate immune system has been a legitimate therapeutic strategy for some years. TLRs 3, 4, 7, 8 and 9 are all validated targets for cancer and a number of companies are developing agonists and vaccine adjuvants. TLR7 in particular has established proof-of-concept as a target in the topical treatment of bladder and skin cancers. However, the development of systemic treatments targeting TLR7 for most other cancers has proved difficult owing to cardiotoxicity or myelosuppression. Tantalisingly, recent animal data have demonstrated that a new class of modified TLR7 agonists can be administered systemically with a good toxicology profile, opening up this target in therapeutic interventions for systemic cancers.