New Insights on Lymphoma Resistance and Targeted Therapies

A recent review published in the journal Oncoscience on October 13, 2025, examines the complex mechanisms through which lymphomas develop resistance to modern cancer therapies. Authored by researchers Bishal Tiwari, Roshan Afshan, and Shruthi Sridhar from Nassau University Medical Center and Detroit Medical Center Wayne State University, the article titled “Targeted therapies and resistance mechanisms in lymphoma: Current landscape and emerging solutions” offers a comprehensive overview of the challenges faced in treating these blood cancers.

Lymphomas rank among the most prevalent blood cancers globally. Advances in treatment, particularly with targeted therapies like monoclonal antibodies, CAR T-cell therapy, and immune checkpoint inhibitors, have significantly improved patient outcomes. These therapies target specific markers present on cancer cells, enhancing their effectiveness. Despite these advancements, many patients experience relapse as their cancers adapt and develop resistance to treatment.

The review identifies four primary mechanisms of resistance that lymphomas exhibit. These include the loss of target antigens, such as CD19 and CD20, mutations that reactivate growth and survival pathways, alterations in the tumor microenvironment that inhibit immune responses, and genetic changes that enable cancer cells to evade apoptosis. Such resistance factors complicate the long-term management of the disease, rendering standard treatments less effective.

“We comprehensively evaluate FDA-approved targeted agents, including monoclonal antibodies (rituximab, brentuximab vedotin, obinutuzumab, mogamulizumab), immune checkpoint inhibitors (nivolumab, pembrolizumab), CAR T-cell therapies (axi-cel, tisa-cel, liso-cel, brexu-cel), bispecific T-cell engagers (mosunetuzumab, epcoritamab), and small-molecule inhibitors (ibrutinib, idelalisib, venetoclax),” the authors note, emphasizing the breadth of their review.

Exploring Innovative Treatment Strategies

In response to the growing issue of treatment resistance, researchers are investigating novel therapeutic approaches. These strategies include combination therapies that target multiple pathways simultaneously, the development of CAR T cells capable of recognizing several antigens, and next-generation antibody therapies designed to enhance effectiveness.

The review also highlights the potential of biomarker-guided therapy, which tailors treatments based on molecular testing of a patient’s unique cancer characteristics. One promising avenue is the implementation of “dual-target” therapies, which aim to complicate the ability of lymphoma cells to develop resistance. Additionally, efforts to bolster the immune system’s response or to re-sensitize resistant tumors are under exploration.

Some of these innovative strategies are already undergoing clinical trials, while others remain in the developmental phase. The review provides valuable insights into the obstacles that current lymphoma treatments face and the innovative solutions being pursued to overcome these hurdles.

By detailing both the biological underpinnings of drug resistance and emerging therapeutic options, this article serves as an important resource for clinicians, researchers, and healthcare professionals dedicated to improving outcomes for patients battling difficult-to-treat lymphoma. The findings underscore the ongoing need for research and development in the fight against this pervasive disease.

For more details, refer to the article by Tiwari et al. in Oncoscience, available at doi: 10.18632/oncoscience.633.