Journal of Medicine, Radiology, Pathology & Surgery (2015), 1, 1–2 Journal of Medicine, Radiology, Pathology & Surgery ● Vol. 1:6 ● Nov-Dec 2015 1 EDITORIAL Targeted therapy for oral submucous fbrosis - Future strategies This editorial is with the objective of igniting the research minds of the specialists treating “oral submucous fbrosis (OSMF),” a chronic debilitating and potentially malignant condition of the oral cavity. Though the etiology of OSMF is multifactorial, the most accepted pathway of pathogenesis is dysregulation of collagen synthesis and degradation pathway [1] similar to many other fbrosing conditions explored in the medical literature. This study sketches some of the successful trials that can possibly help in the successful management of advanced cases. Possible Therapeutic Interventions for OSMF Current management of OSMF includes the abstinence of habits, along with some of the possible interventions include: 1. Blocking the chronic infammatory process by anti- infammatory or immunomodulatory drugs 2. Blocking transforming growth factor-beta (TGF-β) action by antibodies or peptide mimetics of soluble TGF-β receptors 3. Copper chelators like penicillamine to block lysyl oxidase (LOX) activity and prevent cross-linking and other anti-LOX drugs that prevent its action 4. Collagenase activators like colchicine to promote collagen degradation. Probably a combination therapy of the above-mentioned drugs intervening at multiple points along the pathway might be successful. The current research trend to be more focused on antifbrotic or antifbrogenic agents such as pirfenidone, interferon (IFN) and certain blood-pressure-lowering medications [2] to suppress the aberrant scarring process seen in other fbrotic diseases such as idiopathic pulmonary fbrosis, radiation-induced scarring, wherein the pathway found to be similar to OSMF. Pirfenidone (Esbriet, InterMune) is an immunosuppressant that is thought to have anti-infammatory and antifbrotic efects. It efects by suppressing fbroblast proliferation, reducing the production of fbrosis-associated proteins and cytokines and reducing the response to growth factors such as TGF-β and platelet-derived growth factor. Pirfenidone has a UK marketing authorization for the treatment of mild-to-moderate idiopathic pulmonary fbrosis in adults. [3] IFN-gamma is an immunoregulatory cytokine that directly prevents fbroblast proliferation and collagen synthesis. The clinical trials using ã-IFN treatment showed improvements in the patients’ mouth opening with a net gain of 8 ± 4 mm (42%) in the interincisal distance and a range of 4-15 mm, need to be confrmed by further studies. [3] Antihypertensive agents afect the myofbroblasts that produce more angiotensin (ANG) II and active TGF-β which has been described as an ANG/(TGF)-β1 autocrine loop. Anti- hypertensives like Enalapril, losartan that produce inhibition of ANG II or its receptors have been proved to be promising in lung fbrosis. [2,4] Biologic agents - Monoclonal antibodies inhibit the cytokines like TGF-β, tumor necrosis factor-alpha (TNF-α), and connective tissue growth factors that activate infammation. To mention a few, anti-TNF-α antibody infiximab indirectly regulates platelet endothelial adhesion molecule-1 gene expression in two models of in vitro blood cell activation. Infiximab also found to reduce the radiation-induced scarring in the experimental animals. [5] The researchers have studied expression of Insulin-like growth factor, matrix metalloproteinase, nuclear factor kappa-B, studies of genetic predisposition and chromosome or DNA instability etc., however further studies are needed to confrm these risk factors in OSMF, interventions are yet to be proved. Now the need of an hour is stepping towards the pathogenesis based treatment strategies as interventional, multiphasic randomized clinical trials that could help in the successful management of well-established cases of OSMF and preventing its malignant transformation. L. Ashok, G. P. Sujatha Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davanagere, Karnataka, India. Email: ashok_l2002@yahoo.co.in doi: 10.15713/ins.jmrps.36 References 1. Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fbrosis – A collagen metabolic disorder. J Oral Pathol Med 2005;34:321-8. 2. Rafi R, Juarez MM, Albertson TE, Chan AL. A review of current and novel therapies for idiopathic pulmonary fbrosis. J Torac Dis 2013;5:48-73.