Targeted Therapy in Hodgkin Lymphoma: A Promising Frontier

Hodgkin lymphoma (HL), a type of cancer characterized by the presence of Reed-Sternberg cells, has experienced notable advancements in treatment. Traditionally, HL has been treated with chemotherapy and radiation, but these methods can have severe side effects, such as fatigue, nausea, hair loss, and an increased risk of infections, secondary cancers, and other long-term health issues. A promising development in HL treatment is targeted therapy, which focuses on attacking cancer cells specifically, thus reducing side effects. Targeted therapies utilize molecular pathways critical for cancer cell survival and proliferation, unlike traditional chemotherapy that affects all rapidly dividing cells. Brentuximab Vedotin (Adcetris) is a key targeted therapy for HL. It is an antibody-drug conjugate targeting the CD۳۰ protein, highly expressed on Reed-Sternberg cells. Brentuximab Vedotin binds to CD۳۰, allowing a cytotoxic agent, monomethyl auristatin E (MMAE), to be released inside the cancer cell, disrupting its microtubule network, inhibiting cell division, and inducing apoptosis. This therapy has proven effective for patients with relapsed or refractory HL and is often used in combination with other therapies or as maintenance treatment post-transplant. Checkpoint inhibitors like Pembrolizumab (Keytruda) and Nivolumab (Opdivo) represent another significant advancement. These immunotherapies block the programmed death-۱ (PD-۱) pathway, which cancer cells exploit to evade the immune system. By preventing the interaction between the PD-۱ receptor on T cells and its ligands (PD-L۱ and PD-L۲) on HL cells, checkpoint inhibitors restore the immune system's ability to recognize and attack cancer cells. They have shown particular effectiveness in patients with relapsed or refractory HL. Research into small molecule inhibitors targeting specific signaling pathways, such as JAK/STAT and NF-κB, is ongoing. These pathways are crucial for the survival of HL cells. For instance, JAK inhibitors block the JAK/STAT pathway, often activated in HL due to mutations or cytokine overexpression, while NF-κB inhibitors prevent the transcription of genes essential for cell survival. Although still under investigation, these small molecules hold promise for patients unresponsive to conventional therapies. Targeted therapies are advantageous due to their specificity, minimizing damage to normal tissues and allowing for higher doses or longer treatment durations, enhancing efficacy without increasing toxicity. However, cancer cells can develop resistance to targeted therapies through mutations or alternative signaling pathways. Therefore, developing combination therapies and second-line agents is crucial to overcome resistance. Identifying predictive biomarkers is also essential for selecting patients most likely to benefit from these treatments. Combining targeted therapies with traditional treatments may enhance efficacy and prevent resistance. Clinical trials are exploring various combinations to find the most effective regimens. Targeted therapy represents a significant advancement in HL treatment, offering a more effective and less toxic alternative to traditional treatments by focusing on specific molecular mechanisms. As research progresses, the development of new targeted agents and combination strategies promises improved outcomes for patients with HL, ultimately increasing cure rates and enhancing the quality of life for those affected by this challenging disease.

کلیدواژه ها:

Hodgkin lymphoma (HL) ، Targeted therapy ، Brentuximab Vedotin ، Predictive biomarkers