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.
Highlights
Non-Hodgkin lymphomas comprise a heterogenous group of mature lymphoproliferative malignancies that arise as a result of malignant transformation during the process of lymphocyte differentiation and clonal expansion in secondary lymphoid organs [1,2]
It soon became evident that combinations of cytostatic agents, namely cyclophosphamide and vincristine (Oncovin), were more effective compared to the respective monotherapies, because of additive anti-tumor activity of drugs A and B, but in the first place, because A plus B led to synthetic lethality with anti-lymphoma synergy capable of inducing first durable remissions in at least some lymphoma patients [4]
The discovery of anthracycline antibiotics in the early eighties and subsequent addition of hydroxydaunorubicin to COP resulted in the generation of the golden combination of genotoxic agents called CHOP, which have been used for the therapy of non-Hodgkin lymphomas up to the present [5]
Summary
Non-Hodgkin lymphomas comprise a heterogenous group of mature lymphoproliferative malignancies that arise as a result of malignant transformation during the process of lymphocyte differentiation and clonal expansion in secondary lymphoid organs [1,2]. Lymphomas comprise indolent, aggressive, and highly-aggressive malignancies with different treatment approaches and prognosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
