Drug Resistance in Non-Hodgkin Lymphomas

Abstract

Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.

S100A8 promotes chemoresistance via augmenting autophagy in B‑cell lymphoma cells

“…However, drug resistance of lymphoma cells often renders chemotherapy ineffective and greatly shortens the long-term event-free survival of the patients. Therefore, overcoming the drug resistance of lymphoma cells is a major challenge for BCL treatment ( 5 , 40 ). In the present study, the BCL cell lines Daudi, SUDHL-4 and JeKo-1 were examined, which represent Burkitt's lymphoma, diffuse large B-cell lymphoma and mantle cell lymphoma, respectively, and account for 70–85% of all BCLs.…”

“…Haematological malignancies comprise a group of heterogeneous tumours with prominent proliferative and self-replicating abilities (1)(2)(3)(4). Despite advances in treatment, the quality of life of the patients following treatment is highly affected by chemotherapy resistance, which severely impedes the clinical treatment of B-cell lymphomas (BCLs) (5)(6)(7). BCLs comprise a heterogenous group of mature lymphoproliferative malignancies that are among the top 10 causes of cancer-related mortality, mainly occurring in the lymph nodes, spleen, thymus and other lymphoid organs (4,8,9).…”

“…BCLs comprise a heterogenous group of mature lymphoproliferative malignancies that are among the top 10 causes of cancer-related mortality, mainly occurring in the lymph nodes, spleen, thymus and other lymphoid organs ( 4 , 8 , 9 ). Almost all anti-lymphoma treatments are accompanied by chemotherapy resistance, including resistance to genotoxic agents, monoclonal antibodies, antibody-drug conjugates, targeted agents or multidrug combinations ( 5 , 10 – 12 ). Chemotherapy resistance has become the most important challenge to the successful treatment of BCLs.…”

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

“…For a more in depth reading of skin cancer resistance to targeted therapies there are several recent reviews [350,351].…”

Drug Resistance in Hematological Malignancies

“…This special Issue of IJMS encompass twelve articles dedicated to providing an update of mechanisms of resistance to therapies (from conventional treatments to targeted and immunotherapies) in the course of treatment of hematological malignancies [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. It also covers some of the mechanisms by which alterations of biochemical or signaling pathways can be therapeutically exploited to improve therapies.…”