胰腺癌新疗法、诊断方法和流行病学的发展

IF 2.9 4区 医学 Q2 PATHOLOGY
Mohd Haris Jamal , MD Nasiruddin Khan
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引用次数: 0

摘要

胰腺癌仍然是最致命的恶性肿瘤之一,其特点是晚期诊断,侵袭性生物学,对传统治疗有相当大的抵抗力。尽管对分子机制的理解有所改善,治疗方法也有所创新,但总体生存率仍然很低:不到9% %的患者存活超过5年。到2030年,由于化疗耐药、快速转移扩散和有限的有效免疫治疗选择,预计PC将成为美国癌症相关死亡的第二大原因。本文综述了该领域的最新进展,包括流行病学、危险因素、诊断工具和新兴生物标志物。遗传和分子图谱的最新进展为胰腺癌提供了重要的信息。它已经确定了KRAS、TP53、CDKN2A和SMAD4等基因中的关键突变,这些突变在导致这种疾病的过程中起着重要作用。这些发现为探索针对这些突变的新型靶向治疗提供了动力。此外,结合循环肿瘤细胞、循环肿瘤DNA和外泌体的液体活检技术的进步为早期诊断、治疗反应监测和微小残留疾病的检测带来了巨大的希望——任何一项都可能从根本上改变PC的管理。虽然治疗晚期PC的选择非常有限,但唯一潜在的治疗方法是手术,但只有10 - 15% %的患者被诊断为可能可切除的疾病。研究人员正在寻找新的方法来帮助更多的病人有资格接受手术。这包括在手术前使用化疗和放疗来缩小肿瘤的大小。新的化疗方法,如FOLFIRINOX(包括5-氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂)已经改善了一些患者的结果,但它们仍然会引起严重的副作用。免疫疗法虽然在其他癌症中具有革命性,但由于肿瘤的免疫抑制微环境,在PC中取得的成功有限。研究人员正在研究将免疫检查点抑制剂与化疗、放疗和靶向周围组织的药物一起使用,以改善人体的免疫反应。CAR-T细胞和TILs等过继细胞疗法的个性化方法也令人相当兴奋,这些疗法的早期试验证据表明可能有效。人们也在尝试解决肿瘤的致密结缔组织间质,这是PC的特征。到目前为止,在实验室测试中,可以对抗耐药性的药物或可能影响肿瘤环境、阻止周围组织变化、改善药物递送方式的新药已经显示出一些潜力。基于纳米颗粒的药物递送系统也正在被开发,以提高化疗的生物利用度和靶向递送。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Developments in pancreatic cancer emerging therapies, diagnostic methods, and epidemiology
Pancreatic cancer is still one of the deadliest malignancies, characterised by late-stage diagnosis, aggressive biology, and considerable resistance to conventional treatments. Despite improvements in understanding the molecular mechanisms and innovations in treatment, the overall survival remains abysmal: fewer than 9 % of patients survive beyond 5 years. By 2030, PC is predicted to become the second leading cause of cancer-related deaths in the U.S. owing to chemoresistance, rapid metastatic spread, and limited effective immunotherapeutic choices. This review highlights current progress in this field, including epidemiology, risk factors, diagnostic tools, and emerging biomarkers. Recent progress in genetic and molecular profiling has provided important information about pancreatic cancer. It has identified key mutations in genes like KRAS, TP53, CDKN2A, and SMAD4 that play a major role in driving the disease. Such revelations have provided the impetus to explore novel targeted therapies against these mutations. Furthermore, the advances in liquid biopsies incorporating circulating tumour cells, circulating tumour DNA, and exosomes hold substantial promise for early diagnosis, treatment response monitoring, and detection of minimal residual disease—any of which could radically transform PC management. While very limited options for the treatment of advanced-stage PC remain, the only potential curative treatment is surgery, yet only 10–15 % of patients are diagnosed with potentially resectable disease. Researchers are looking into new methods to help more patients qualify for surgery. This involves using chemotherapy and radiotherapy to reduce the size of the tumor before the operation. New chemotherapy treatments like FOLFIRINOX (which includes 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) have improved results for some patients, but they can still cause significant side effects. Immunotherapy, though revolutionary in other cancers, has had limited success in PC due to the tumour's immunosuppressive microenvironment. Researchers are looking into using immune checkpoint inhibitors together with chemotherapy, radiation, and drugs that target the surrounding tissue to improve the body's immune response. There is also considerable excitement surrounding personalised approaches with adoptive cell therapies such as CAR-T cells and TILs, which are trialled with early evidence of potential efficacy. Attempts are also being made to address the dense desmoplastic stroma of the tumour that characterises PC. Drugs that can fight resistance or new medicines that might affect the tumor environment, stop changes in surrounding tissues, and improve how drugs are delivered have shown some potential in laboratory tests so far. Nanoparticle-based drug delivery systems are also being developed to improve the bioavailability and targeted delivery of chemotherapy.
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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
405
审稿时长
24 days
期刊介绍: Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.
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