最近在理解外周 T 细胞淋巴瘤 (PTCL) 方面取得的进展验证并拓宽了我们的视角，强调了它们的多样性性质以及实体背后不同的分子机制。基于全面积累的理解，PTCL 目前克服了任何疾病最具挑战性的特征：稀有性、令人难以置信的异质性以及缺乏任何既定的护理标准。前线部署的治疗方法是从针对其他疾病开发的治疗方案中推断出来的。最近批准的三种药物 brentuximab vedotin (BV)、pralatrexate 和 belinostat 用于治疗复发或难治性疾病患者，提供了有关病理生理学和未来方向的线索，尽管满足这些加速批准的上市后要求 (PMR) 的挑战导致了其中一种药物被撤回，另两种药物面临危险。一线治疗方案的编辑通常称为 CHOP（环磷酰胺、阿霉素、长春新碱和泼尼松）+ 方法，看起来更像是 CHOP-减策略，因为五种药物治疗方案的毒性通常会降低添加的剂量强度。新颖的药物，使任何进展的希望都化为泡影。上述所造成的领域动荡，加上不断变化的分类，让该领域对前进的道路充满了不确定性。尽管存在这些挑战，新药物方法研究的经验发现，加上 PTCL 淋巴瘤发生研究中出现的逻辑，已经开始阐明（尽管对某些人来说还很模糊）一个潜在的方向。针对 PTCL 表观基因组离散成分的药物的经验发现，再加上控制表观遗传生物学的基因中多个突变的描述，至少提供了一个最终由假设驱动的机会。最近的认识是，唯一能显着改善复发性疾病患者无进展生存期 (PFS) 的药物组合是基于表观遗传生物学不同且离散成分的双重靶向的药物组合，这已经建立了绕过化疗添加研究的可能性。既合理又可行，而且可能是这种疾病取得量子进展的最佳前景。在此，我们通过 2025 年的视角来分析 PTCL，突出并强调了阻碍进步的墙壁。我们将批判性地探索 PTCL 研究的所有线索和全景。版权所有 © 2024。由 Elsevier Ltd 出版。

Recent advancements in comprehending peripheral T-cell lymphomas (PTCLs) validate and broaden our perspective, highlighting their diverse nature and the varying molecular mechanisms underlying the entities. Based on a comprehensive accumulated understanding, the PTCLs currently overcome the most challenging features of any disease: rarity, incredible heterogeneity, and a lack of any established standard of care. The treatments deployed in the front-line are extrapolated from regimens developed for other diseases. The recent approval of the three drugs brentuximab vedotin (BV), pralatrexate, and belinostat for patients with relapsed or refractory disease has provided clues about pathophysiology and future directions, though challenges satisfying post-marketing requirements (PMR) for those accelerated approvals have led to one of those drugs being withdrawn and put the other two in jeopardy. Edits of the front-line regimens, often called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-plus approaches, look more like CHOP-minus strategies, as the toxicity of five-drug regimens often reduces the dose intensity of the added 'novel' drug, nullifying any hope of an advance. The turmoil in the field produced by the aforementioned, coupled with an ever-changing classification, has left the field uncertain about the path forward. Despite these challenges, empiric findings from studies of novel drug approaches, coupled with a logic emerging from studies of PTCL lymphomagenesis, have begun to illuminate, albeit faintly for some, a potential direction. The empiric finding that drugs targeting the discrete components of the PTCL epigenome, coupled with the description of multiple mutations in genes that govern epigenetic biology, offers, at the very least, an opportunity to finally be hypothesis-driven. The most recent recognition that the only combination of drugs shown to markedly improve progression-free survival (PFS) in patients with relapsed disease is one based on dual targeting of different and discrete components of that epigenetic biology has established a possibility that circumnavigating chemotherapy addition studies is both plausible, feasible, and likely the best prospect for a quantum advance in this disease. Herein, we analyze PTCL through a 2025 lens, highlighting and underscoring walls that have impeded progress. We will critically explore all the clues and the panoramic view of PTCL research.Copyright © 2024. Published by Elsevier Ltd.