Abstract PO-011: Role of tumor heterogeneity, tumor microenvironment and tumor initiating cell in gastric carcinogenesis from the perspective of development of hypothesis for its clinical application

Abstract

Abstract Gastric Cancer (GC) is one of the most malignant type of cancer due to its rapid progression, distant metastasis and resistant to conventional chemotherapy. This study is to search the development towards specific therapy to overcome conventional chemotherapy resistance and probable hypothesis to develop it. It is known that tumor heterogeneity plays a fundamental essential role in cancer development and chemo resistance. Gastric Carcinoma Tumor initiating cell (GATIC) controls high tumerogenicity, maintenance of self renewal potential, formation of cancer and non cancer cells and chemotherapy resistance. Identifying the putative specific cell marker for purification and functional validation of GATIC, tracing the origin of GATIC, decoding the regulatory mechanism of GATIC, pave the way for the development of GATIC targeted therapy which is in phase of preclinical study and clinical trial. Alteration of tumor microenvironment is deeply implicated in tumor progression and metastasis in gastric cancer patient. Interaction between tumor cell and their microenvironment with cytokines and miRNA in extracellular vesicles such as exosome can have a substantial impact on tumor characteristics. Interaction and its clinical impact of alteration of GC microenvironment will be discussed. In the possible treatment hypothesis the level IL6, M1, CXCl12/CXCR may be blocked and the level of M2, C8+T cell and CCK2R may be amplified to develop TEM directed targeted therapy. After uncovering the mechanism of chemo resistance the differentiation therapy and elimination therapy of gastric carcinoma may be a sustainable targeted therapy. In this context over expression of ATOH1 in GATICS and Lentiviral vector based knockdown of PGK1 may be a treatment method to overcome Chemo resistance of GC. In the way of elimination therapy Cyclopamine and Vismodegib may be a feasible targeted therapy in GC. molecules which is specific suppressor of Wnt/B catenin may be used as a selective therapy for GATIC. Citation Format: Kalyan Kusum Mukherjee, Dattatreya Mukherjee. Role of tumor heterogeneity, tumor microenvironment and tumor initiating cell in gastric carcinogenesis from the perspective of development of hypothesis for its clinical application [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-011.