卵巢癌化疗耐药机制的研究进展

卵巢癌是女性生殖系统常见的恶性肿瘤之一,由于缺乏特异性临床表现及早期诊断方法,多数患者确诊时已为晚期,病死率居妇科恶性肿瘤首位。化疗作为卵巢癌的主要治疗方法,虽然多数患者初始反应敏感,甚至可达到近期缓解,但是由于化疗耐药的产生,最终导致治疗失败或死亡,严重影响了卵巢癌患者的远期疗效和总体生存率。因此,深入研究卵巢癌的耐药机制,寻找有效干预靶点,成为改善化疗效果和解决耐药问题的关键。本文就卵巢癌化疗耐药机制的相关研究综述如下。     

黄酮类化合物逆转肿瘤多药耐药作用的研究进展

肿瘤多药耐药是肿瘤治疗过程中一个亟待解决的难题,其表现为肿瘤细胞对单一或多种化疗药物同时出现耐药性,从而导致治疗失败,与药物的化学结构和作用机制无关。将化疗药物与肿瘤多药耐药逆转剂联合应用是目前公认的治疗方案之一。黄酮类化合物由于其低毒、高效,具有多种药理作用等优点而受到广泛的关注。在肿瘤治疗期间,黄酮类化合物能通过抑制ABC转运体、诱导凋亡、调节氧化应激等作用逆转肿瘤多药耐药。归纳总结了黄酮类化合物逆转肿瘤多药耐药的主要机制、应用及其纳米剂型改造的进展,为进一步的临床研究提供参考。     

黄酮类化合物对肿瘤多药耐药调节作用的研究进展

多药耐药是临床上化疗失败的重要原因之一。黄酮类化合物存在于多种植物中,具有广泛的药理活性,对P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、乳腺癌耐药蛋白(BCRP)等外向转运蛋白的抑制作用使其可能成为肿瘤多药耐药调节剂。文中分别对黄酮类化合物对ABC家族转运蛋白抑制作用的研究概况、作用机制以及构效关系进行综述,为肿瘤多药耐药抑制剂的开发和应用提供重要信息。     

黄酮类化合物逆转肿瘤多药耐药的研究进展

肿瘤多药耐药(multidrug resistance,MDR)是临床上导致化疗失败的重要原因。采用化疗药物与多药耐药逆转剂联合给药是逆转多药耐药的非常具有前景的策略。目前黄酮类化合物在逆转多药耐药上显示出较大潜力。黄酮类化合物可以通过抑制外排蛋白、诱导凋亡、调节细胞周期以及调节细胞内氧化应激等发挥逆转耐药的作用。黄酮类化合物可以单独给药或与化疗药物等联合给药用于逆转肿瘤多药耐药。本文就黄酮类化合物逆转MDR的机制及应用研究进展进行综述。     

铂耐药卵巢癌的免疫治疗研究进展

卵巢癌是女性生殖系统疾病中死亡率最高的恶性肿瘤,大多数患者发现时已处于晚期。虽然经过满意的肿瘤细胞减灭术联合以铂类为基础的化疗可以达到临床缓解,但大多数患者会在最初治疗后数年内复发,继而死亡。化疗耐药和免疫逃逸可能是导致卵巢癌治疗失败的重要原因之一,因此迫切需要新的治疗策略来改善患者的临床结局。本文阐述了免疫治疗在铂耐药卵巢癌治疗中的研究进展。     

一类抗肿瘤新药洛铂治疗卵巢癌研究进展

卵巢癌是女性常见恶性肿瘤之一,具有病情隐匿、易转移、预后差等特点。化疗在卵巢癌综合治疗中占有重要地位,其中紫杉醇联合卡铂方案是近20年来循证医学证据最充分的一线标准方案。但是,由于卡铂具有严重骨髓抑制、治疗诱导性耐药以及与顺铂高度交叉耐药等缺点,限制了其在临床长期、广泛地应用。因此,积极探索"高效、低毒、不交叉耐药"的新型铂类药物及其联合化疗方案,是进一步提高卵巢癌疗效的重要途径之一。本文仅就第3代铂类抗肿瘤药     

激素类基因与卵巢癌耐药关系的研究进展

近年来,关于多药耐药性的研究越来越多,而关于多药耐药基因的研究已成为目前化疗药物耐药机制研究的重要方面,多药耐药基因、P-糖蛋白介导的卵巢癌耐药是当前研究的热点,近些年已开展了一系列关于激素类基因与卵巢癌耐药关系的实验研究。本文综述了激素类基因与卵巢癌耐药关系的研究进展。     

卵巢癌术后应用联合化疗的观察与护理

卵巢癌是妇科恶性肿瘤之一，死亡率高，愈后差，如果治疗方法得当，不仅可以延长生命，而且可以达到治愈效果。卵巢癌以手术治疗为主，配合化疗是治疗的主要辅助手段，术后化疗配合护理至关重要，即使广泛转移也能取得一定的疗效。铂化合物被广泛应用于妇科肿瘤的化疗，并...     

黄酮类化合物抗肿瘤作用研究进展

黄酮类化合物是广泛存在于自然界中的一类多酚化合物,有极其丰富的药理活性。最新研究表明,天然以及人工合成的黄酮表现出显著的抗肿瘤活性;并且一些黄酮组合应用时会引起抗肿瘤效果改变;另外一些天然黄酮及查耳酮衍生物都表现出逆转多药耐药的活性。这些研究为临床肿瘤治疗提供新的思路,黄酮类化合物也可以作为一种潜在的肿瘤治疗辅助药物。综述近年来天然以及合成的flavopiridol、佩兰素等黄酮类化合物抗肿瘤作用机制、多药耐药逆转活性以及构效关系的研究进展。     

莪术油与SKOV-3和SKOV-3/DDP增殖的量效时效关系

<正>卵巢癌是女性生殖系统常见的三大恶性肿瘤之一,其致死率居妇科恶性肿瘤之首~[1],已成为严重威胁女性生命健康的疾病。卵巢癌治疗以手术为主,辅以放、化疗。又因卵巢癌早期诊断困难,疾病进展迅速,确诊时多属晚期,故其治多依赖化疗。然而化疗药物毒副作用大,化疗耐药常致卵巢癌高复发率、高病死率。研究显示即使初次治疗有效率可达70%,很多患者仍因耐药导致复发、死亡~[2]。美国国立癌症研究所监测流行病学及结果数据库资料显示,近30年卵巢癌5年生     

小分子靶向抗肿瘤药物耐药机制与应对策略

癌症是危害人类健康的重要因素,并已经成为全球第二大致死病因。随着小分子靶向抗癌药物的出现与广泛应用,癌症的治愈率与患者的生存期均显著提高。但肿瘤耐药问题随之而来,大部分小分子靶向抗肿瘤药物在应用一段时间后会出现不同程度的耐药现象。深入研究小分子靶向抗癌药物的耐药机制是寻找克服肿瘤耐药策略的必经之路。通过对小分子靶向抗癌药物常见的一些耐药机制进行总结,并提出了一些相应的克服肿瘤耐药的策略,以期为相关药物研发提供一定的参考。     

真菌耐药的现状与对策

真菌耐药的报道日益增多，目前的研究一方面进一步探讨真菌产生耐药的机制、传播方式、耐药性与临床治疗的关系，以及建立标准化抗真菌药物敏感试验，从而控制耐药性的进一步发展；另一方面加快开发新的抗真菌药物，以应对日益增多的耐药真菌。     

Overcoming drug resistance in pancreatic cancer

Introduction: Pancreatic cancer has the worst survival rate of all cancers. The current standard care for metastatic pancreatic cancer is gemcitabine, however, the success of this treatment is poor and overall survival has not improved for decades. Drug resistance (both intrinsic and acquired) is thought to be a major reason for the limited benefit of most pancreatic cancer therapies.

Areas covered: Previous studies have indicated various mechanisms of drug resistance in pancreatic cancer, including changes in individual genes or signaling pathways, the influence of the tumor microenvironment, and the presence of highly resistant stem cells. This review summarizes recent advances in the mechanisms of drug resistance in pancreatic cancer and potential strategies to overcome this.

Expert opinion: Increasing drug delivery efficiency and decreasing drug resistance is the current aim in pancreatic cancer treatment, and will also benefit the treatment of other cancers. Understanding the molecular and cellular basis of drug resistance in pancreatic cancer will lead to the development of novel therapeutic strategies with the potential to sensitize pancreatic cancer to chemotherapy, and to increase the efficacy of current treatments in a wide variety of human cancers.     

晚期非小细胞肺癌EGFR-TKIs获得性耐药后治疗策略研究进展

肺癌是癌症相关死亡的首要原因。非小细胞肺癌（NSCLC）约占肺癌的85%,且患者在诊断时大多为晚期。随着表皮生长因子受体（EGFR）在肺癌中被发现,针对特定基因突变的靶向治疗成为晚期NSCLC的重要治疗方式,并显著延长了患者生存期。尽管第一、二、三代EGFR-酪氨酸激酶抑制剂（TKI）蓬勃发展,但随着治疗时间的推移,患者都可能面临耐药和进展。为克服这一难题,基于耐药机制的相关治疗策略正在研究中。本文旨在对近年来EGFR-TKIs,特别是在疗效及安全性上作为指南更优推荐的第三代EGFR-TKIs的耐药机制和治疗策略的研究进展进行综述。     

New ABC transporters in multi-drug resistance

ATP-binding cassette (ABC) transporters have been the subject of intense scrutiny as potential mediators of clinical drug resistance. Since the identification of MDR1/P-glycoprotein over 15 years ago, it has been recognised that reduced intracellular accumulation of anticancer agents can result in significant degrees of drug resistance. The multi-drug resistance associated protein (MRP1) was the second ABC transporter to be associated with drug resistance, and in the past three years, five additional MRP family members have been recognised. While studies to define the substrate specificity and normal physiology for the new transporters is underway, it appears that the principal function for P-glycoprotein and MRP is protection of the host from xenobiotics. The most recent addition to the list of ABC transporters mediating drug resistance is the half-transporter, MXR/BCRP/ABCP. Overexpression of this transporter is associated with mitoxantrone, anthracycline and camptothecin resistance. The discovery of multiple distinct ABC transporters capable of conferring multi-drug resistance offers the possibility that clinical reversal of drug resistance can be achieved. Studies with P-glycoprotein inhibitors alone have generated mixed results; one potential explanation is that other transporters may be co-expressed. These additional transporters offer new therapeutic targets, as both specific and multi-specific inhibitors should be identified for clinical trials in drug resistance reversal.     

Nano-based strategies to overcome p-glycoprotein-mediated drug resistance

Introduction: The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution. It extrudes several agents out of cells, arising MDR and decreasing the bioavailability of drugs. Hence, cancer cells become insensitive to chemotherapy.

Areas covered: Many agents have been developed to reverse MDR, but it is difficult to deliver them into cancer sites and cancer cells. The emerging nano-based drug delivery systems have been more effective to overcome P-glycoprotein-mediated MDR by increasing the intracellular delivery of these agents. Here, we represent systems including siRNA-targeted inhibition of P-gp, monoclonal antibodies, natural extracts, conventional inhibitors, hard nanoparticles and soft nanoparticles as delivery systems in addition to a novel approach applying cell penetrating peptides.

Expert opinion: Overcoming cancer drug resistance using innovative nanotechnology is being increasingly used and developed. Among resistance mechanisms, drug efflux transporter inhibitors and MDR gene expression silencing are among the those being investigated. In the near future, it seems some of these nanomedical approaches might become the mainstay of effective treatment of important human conditions like cancer.     

PARP抑制剂在肿瘤治疗中的研究进展

肿瘤是威胁人类生存与健康的重要原因之一。在肿瘤的药物治疗中,化疗是常用手段之一,但由于其特异性低、不良反应大、长期使用易产生耐药性等问题,应用受到较大限制。基于DNA损伤修复机制开发的新型抗肿瘤药物聚腺苷酸二磷酸核糖聚合酶(poly-ADP ribose polymerase,PARP)抑制剂可能是解决这一问题的关键。PARP抑制剂是一类靶向抑制PARP-1蛋白,诱导BRCA基因突变的肿瘤细胞发生“合成致死”现象的新型抗肿瘤药物,已成功应用于卵巢癌、乳腺癌等肿瘤的治疗。近年来PARP抑制剂更是与各类一线化疗药、靶向制剂及免疫检查点抑制剂等进行联合治疗,扩大了临床适用范围。本文将对PARP抑制剂的药理作用与作用机制、在肿瘤治疗中的应用及其耐药机制等研究进展进行总结,以期为PARP抑制剂的临床应用提供合理指导。