Lekshmi R Nath

Title : The multifactorial role of transforming growth factor-beta 1 in hepatocellular carcinoma

Abstract:

Transforming growth factor-beta1 (TGF-β 1) is a critical homeostasis regulator aberrantly activated during inflammation, fibrosis, and carcinogenesis. Causative agents of chronic liver diseases, such as viral infection, alcohol, and co-morbidities, such as diabetes and obesity, trigger the release of TGF-β1, which stimulates inflammation, extracellular matrix (ECM) production, and accumulation of fibrous material that eventually progresses to cirrhosis. As fibrosis continues, the interaction of overexpressed TGF-β1 with integrins and other ECM proteins can alter signaling, accumulate gene mutations, and induce epithelial-mesenchymal transition and hepatocarcinogenesis. Among other TGF-β isoforms, significant and progressive expression of TGF-β1 during the entire course of HCC pathogenesis, from chronic hepatitis to HCC, makes it a sensitive and accurate diagnostic marker of HCC. Even after establishing HCC, TGF-β1 increases as HCC progresses and is associated with poor prognosis and shorter survival. Since TGF-β1 is the master regulator of the immunosuppressive tumor milieu in HCC, TGF-β1 inhibition could sensitize ICI, tyrosine kinase inhibitors, and other diagnostic, prognostic, and therapeutic candidates in HCC.

 Audience Take Away:

• Systematic research inputs are essential to establish the Diagnostic-Prognostic-Therapeutic Impact of Transforming Growth Factor-beta 1 in Hepatocellular Carcinoma.
• Our presentation will provide the basic science and relevance of TGF-β1 in the context of HCC, which can be helpful to the audience for postulating novel hypotheses and research strategies.
• HCC remains the deadliest-refractory tumor predominantly due to its delayed diagnosis, poor prognosis and resistance to treatment. TGF-β1 can be validated appropriately along with current biomarkers such as AFP for early diagnosis and importantly, anti-TGF-β1 agents can be developed as combination therapy to sensitize the current therapy regimen. In this context, our presentation will be helpful to the gastroenterology professionals improve the clinical practice.
• As TGF-β1 is a pleotropic cytokine involved in inflammation, fibrosis and carcinogenesis, other faculty can expand their research to evaluate the potential of this target molecule against many pathological conditions as biomarker, drug target, and to design personalized therapy.
• We believe that TGF-β1 can be developed as a sensitive-specific easily measurable biomarker for HCC and therapies targeting TGF-β are being combined with immune check point inhibitors makes the target ideal for drug development as well. So, definitely, our content can make an impact among the oncology clinicians and scientist
• Even though a plethora of supporting evidence is available, still TGF-β1 is not much studied and evaluated compared with other markers such as AFP. By incorporating TGF-β1 in the panel of current biomarker for HCC diagnosis and prognosis can improve the sensitivity of diagnosis, efficacy of treatment and affordable to the society.
• Support the development of novel drug candidate against TGF-Beta
• Development of novel-easy detection techniques for TGF-β1
• Knowledge about the current research about TGF-β1 and HCC
• Challenges in establishing the role of TGF-β1 in HCC clinical management.

Biography:

Dr Lekshmi R. Nath is working as an Associate Professor in the Department of Pharmacognosy at Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, India. She pursued her PhD . under Dr Ruby John Anto, Cancer Research Program, Rajiv Gandhi Centre for Biotechnology (RGCB), Trivandrum, Kerala, an autonomous Research Institution under DBT, Govt: of India. Her Ph.D. findings on hepatocellular carcinoma recently received four international patents US, Canada, Japan & South Korea (WO 2017208254 A1, “Uttroside B and Derivatives Thereof as Therapeutics for Hepatocellular Carcinoma”). The USFDA has recently granted an Orphan drug designation to the small molecule chemotherapeutic Uttroside–B against hepatocellular carcinoma. MOU signed by RGCB with Oklahoma Medical Research Foundation, USA, for the clinical translation of Uttroside B in liver cancer patients and technology transfer carried out with a multi-national company, Q Biomed. She has more than 45 publications and has been invited as a resource person to many national and international conferences. She is the editorial board member and reviewer of high-impact scientific journals. Her current research interest includes the study of signalling events associated with the fatty liver to Hepatocellular carcinoma, elucidating the role of plant-derived pure compounds in cancer chemoprevention, chemosensitization, and chemotherapy. She is also exploring the potential of traditional knowledge for various infectious diseases, their mechanism of action and validation through pre-clinical models.