Abstract
Non-Hodgkin lymphoma (NHL) presents a complex therapeutic challenge due to its heterogeneous nature and the high incidence of relapse following initial treatment. As such, patients who are more susceptible to treatment resistance face a poor prognosis with limited treatment options. With recent advances, the direct targeting of overexpressed gene products is a novel therapeutic approach to overcome resistance mechanisms in unresponsive NHL patients. In the pathogenesis of NHL, we suspect aberrant deregulations amongst three major oncogenes: Yin Yang 1 (YY1), B-cell lymphoma 2 (Bcl-2), and Myelocytomatosis oncogene (c-Myc). Through analyses of the reported literature data, we have determined, indeed, multiple cross-talk signaling pathways (i.e. with factors MDM2, NF-κΒ, SENP1, TGF-β, p53, ERK) for YY1, Bcl-2, and c-Myc that enable malignant cells to evade immune surveillance, promote tumor aggressiveness, and maintain resistance against various treatment modalities. In addition, we also present various approaches and agents to target each of the gene products, with discussion of challenges faced to generate such agents that specifically target the tumor cells.
Overview
- The study focuses on understanding the genetic basis of Non-Hodgkin lymphoma (NHL) and identifying potential therapeutic targets to overcome treatment resistance.
- The researchers analyzed the literature data on the oncogenes YY1, Bcl-2, and c-Myc to identify cross-talk signaling pathways that enable malignant cells to evade immune surveillance and promote tumor aggressiveness.
- The primary objective of the study is to understand the pathogenesis of NHL and to identify novel therapeutic strategies to improve treatment outcomes for unresponsive NHL patients.
Comparative Analysis & Findings
- The study identified multiple cross-talk signaling pathways between YY1, Bcl-2, and c-Myc, which enable malignant cells to evade immune surveillance, promote tumor aggressiveness, and maintain resistance against various treatment modalities.
- The analysis highlights the importance of targeting these oncogenes to overcome treatment resistance in NHL patients.
- The study discusses various approaches and agents to target each of the gene products, including challenges faced to generate such agents that specifically target tumor cells.
Implications and Future Directions
- The findings of this study suggest that targeting the aberrant regulators of YY1, Bcl-2, and c-Myc may lead to novel therapeutic strategies for NHL patients.
- Future studies should focus on developing therapeutic agents that specifically target these oncogenes and their downstream signaling pathways.
- A deeper understanding of the molecular mechanisms underlying NHL pathogenesis will also be essential for identifying new targets and developing more effective treatment strategies.