Mantle cell lymphoma (MCL) is a rare but incurable subtype of B cell non-Hodgkin’s lymphoma. It is characteristic by the initial lymphomagenesis event, t(11;14)(q13;q32), which leads to the overexpression of cyclin D1. Recent advances in the clinical treatments, especially BTK inhibitors and chimeric antigen receptor T (CAR-T) cell therapy, have greatly improved patient survival. However, patients with MCL frequently experience relapses with worse clinical outcome. Therefore, there is an urgent need for new therapeutic targets to overcome the primary resistance and acquired resistance to each therapy. With two decades of experience and expertise of studying drug response and resistance clinically and preclinically, it is understood that MCL cells employ multiple mechanisms involving both tumor cells and tumor microenvironment to promote cancer cell evolution, the development of therapeutic resistance and thus disease progression. These may due to acquisition of resistance-driving genetic mutations, transcription/epigenetic reprogramming leading to compensatory or alternative activation of survival signaling networks, or trigging immune-suppression or evasion. Our preclinical studies mainly focus on the understanding of the mechanisms of resistance to cutting-edge therapies, such as BTK inhibitors and CAR-T therapy, and the development of novel therapeutic strategies to overcome the emerging resistance, for example, MATCH for precision medicine, targeting OXPHOS, BTK-MALT1-axis and TIGIT to overcome resistance to BTK inhibitors and CAR T therapy.
Citation Format: Michael Wang. Preclinical data in MCL [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr IA19.