Recent Findings on the Application of Toll-like Receptors Agonists in Cancer Therapy.
The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs is Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation. With their ability to induce apoptotic response and activation of innate and adaptive immunity, TLRs are an interesting pharmacological target for the development of anticancer therapy. There are numerous studies including the clinical trials reviewed in this paper, indicating that TLR agonists, especially combined with other more conventional therapies such as chemotherapy and radiotherapy, are promising adjuvants or components of newly developed treatment regimens. Still, the increasing number of studies indicating protumorigenic consequences of TLR activation in various cancer types and recent reports of the existence of endogenous TLR ligands, forewarn that more studies on this topic are required before their inclusion into regular clinical practice.
Department of Radiotherapy and Medical Oncology, University Hospital Centre Sisters of Mercy, Zagreb. Croatia.
Martina
M
Mikulandra
Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb. Croatia.
Jasminka
J
Pavelic
Laboratory for Personalized Medicine, Rudjer Boskovic Institute, Bijenicka 54, HR- 10000 Zagreb. Croatia.
Tanja Matijevic
TM
Glavan
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology
D000970:Antineoplastic Agents; D051193:Toll-Like Receptors
Toll-like receptors; agonists; cancer; clinical trials; immunity; therapy