Barriers to achieving a cure in lymphoma

Abstract

Lymphoma is a diverse disease with a variety of different subtypes, each characterized by unique pathophysiology, tumor microenvironment, and underlying signaling pathways leading to oncogenesis. With our increasing understanding of the molecular biology of lymphoma, there have been a number of novel targeted therapies and immunotherapy approaches that have been developed for the treatment of this complex disease. Despite rapid progress in the field, however, many patients still relapse largely due to the development of drug resistance to these therapies. A better understanding of the mechanisms underlying resistance is needed to develop more novel treatment strategies that circumvent these mechanisms and design better treatment algorithms that personalize therapies to patients and sequence these therapies in the most optimal manner. This review focuses on the recent advances in therapies in lymphoma, including targeted therapies, monoclonal antibodies, antibody-drug conjugates, cellular therapy, bispecific antibodies, and checkpoint inhibitors. We discuss the genetic and cellular principles of drug resistance that span across all the therapies, as well as some of the unique mechanisms of resistance that are specific to these individual classes of therapies and the strategies that have been developed to address these modes of resistance.

Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B‐cell lymphomas

“… 1 , 2 The prognosis of most BCL subtypes has been dramatically improved by the advancements of disease subtype‐oriented molecular‐targeted therapeutics, including monoclonal antibodies (MoAbs) and small molecule compounds, which are adapted according to the immunological, genetic, and/or molecular phenotypes. 3 , 4 However, the changes and/or dysregulation of either expression pattern, function, or structure of targeted molecule/pathway in tumor cells directly cause the loss of response to target‐specific agents, 5 , 6 and there remain patients incurable with currently available therapeutics. Thus, further development of effective new therapies, regardless of disease subtypes, is still awaited.…”