实体肿瘤靶向药物疗效评价标准的现状和展望

近几年抗肿瘤靶向药物的研究取得了突破性的进展,基于基因水平的肿瘤分子诊断技术的发展及特异性靶向药物的应用,推动了癌症治疗进入精准医学新时代。传统的肿瘤治疗评价体系如WHO 或RECIST标准不能准确地对靶向药物治疗进行疗效评价,无法准确地反映患者的生存获益,因此,探索并建立适用于肿瘤靶向药物的疗效评价标准迫在眉睫。本文将回顾抗肿瘤药物疗效评价标准发展历史,介绍针对各类肿瘤的不同靶向药物疗效评价标准的发展及演化历程,并重点介绍结合免疫指标评价的新标准,对该新标准的具体定义、指导原则和临床应用进行详细阐述。有理由相信,随着肿瘤靶向药物疗效评价体系的不断完善,会给个体化肿瘤治疗带来新的进展。     

实体瘤疗效评价标准简介

随着靶向治疗时代的到来,新的实体瘤评价标准如改良的实体瘤反应评价标准、正电子发射断层扫描反应标准、Choi 标准和免疫相关反应标准相继出现。血清标志物和循环肿瘤细胞等也用于临床反应的评价。这些指标为肿瘤疗效评价提供了有力的工具。     

肿瘤疗效评价研究进展

肿瘤疗效评价是决定病人继续治疗和研究项目是否继续进行的依据,近10年来．国内外肿瘤疗效评价标准正逐步由传统的实体瘤疗效评价标准向新的综合肿瘤疗效评价标准转化。文章就传统化疗药物、分子靶向药物、中医药等疗效评价研究进展作一综述。     

实体肿瘤疗效评价标准的研究

近十几年来,恶性肿瘤治疗的发展非常迅速,尤其是新抗肿瘤药物的不断涌现,使得许多肿瘤由原来的姑息性治疗进入到了根治性治疗的阶段,而化疗药物及分子靶向药物疗效的提高,使实体瘤疗效评定标准更趋于完善和统一.     

肿瘤的靶向治疗

靶向治疗是针对肿瘤细胞恶性表型的分子靶点,作用于促进肿瘤生长、存活的特异性细胞受体、信号传导等通道,实现抑制肿瘤细胞生长或促进凋亡的抗肿瘤作用。新的靶向治疗药物rituximab、伊马替尼、赫赛汀和全反式维甲酸已开始用于临床治疗,本文综述这些药物的作用机制、适应证、疗效及安全性。与传统细胞毒化疗不同,肿瘤靶向治疗具有特异性抗肿瘤作用,并且毒性明显减少。肿瘤靶向治疗令人鼓舞的初步成果为其进一步发展奠定了基础,提供了典范,开创了肿瘤化疗的新领域。     

磁性药物靶向治疗肿瘤

近年来，随着生物技术、纳米技术和物理化学等多学科的飞速发展，磁性药物靶向治疗有了长足进步。本文对其历史、现状及发展作了简要介绍。     

肿瘤靶向药物疗效及毒性与基因多态性间相关性的研究进展

肿瘤的治疗历来都是医学研究的热点和难点,分子靶向药物的出现为肿瘤的治疗提供了一种新方式,其疗效及毒性一直是人们关注的焦点,但研究发现不同的个体对药物的反应存在较大差异,这可能与基因多态性有关。作者就国内外有关基因多态性与各种常见靶向药物的疗效及毒性间相关性的最新研究进展进行综述。     

肿瘤分子靶向治疗疗效预测因子的研究进展

疗效预测因子检测可能改善肿瘤分子靶向治疗的预后。表皮生长因子受体(EGFR)、棘皮动物微管蛋白样4-间变性淋巴瘤激酶(EML4-ALK)、人表皮生长因子2(HER2)、KRAS、c-kit/PDGFRA和血管内皮生长因子(VEGF)等是肿瘤分子靶向治疗的重要预测因子。     

磁性药物靶向治疗肿瘤

近年来，随着生物技术、纳米技术和物理化学等多学科的飞速发展，磁性药物靶向治疗有了长足进步。本文对其历史、现状及发展作了简要介绍。     

肿瘤疗效影像学评价标准进展

在过去的30年里,出现了许多依赖于影像学的肿瘤疗效评价标准。随着治疗手段的多样化及影像学技术的发展,新的评价标准不断产生。本文将对 WHO 标准、RECIST 标准以及肿瘤靶向治疗评价标准进行综述,并比较它们的区别及阐明各自优势。     

对分子靶向治疗疗效评估的思考

评估肿瘤治疗效果的主要目的在于评价患者是否从抗癌治疗中获益,以确定治疗或临床研究是否继续进行.因此,建立统一的疗效评价指标和标准,将有助于比较不同治疗方案的效果,优选治疗方法.     

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

In 2017, immune response evaluation criteria in solid tumors (iRECIST) were introduced to validate radiologic and clinical interpretations and to better analyze tumor’s response to immunotherapy, considering the different time of following and response, between this new therapy compared to the standard one. However, even if the iRECIST are worldwide accepted, to date, different aspects should be better underlined and well reported, especially in clinical practice. Clinical experience has demonstrated that in a non-negligible percentage of patients, it is challenging to determine the correct category of response (stable disease, progression disease, partial or complete response), and consequently, to define which is the best management for those patients. Approaching radiological response in patients who underwent immunotherapy, a new uncommon kind of target lesions behavior was found. This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug. Therefore, new groups of response have been described in clinical practice, defined as “atypical responses,” and categorized into three new groups: pseudoprogression, hyperprogression, and dissociated response. This review summarizes and reports these patterns, helping clinicians and radiologists get used to atypical responses, in order to identify patients that respond best to treatment.     

分子成像与肿瘤靶向治疗*

肿瘤关键分子靶点的异常表达（表达水平和表达状态）与分子靶向治疗反应、治疗效果及预后密切相关。因此,精准评价肿瘤关键分子表达水平和表达状态,无论在肿瘤分子靶向治疗开展前、过程中以及治疗后均显得尤为关键。分子成像可以无创、实时而全面地对肿瘤关键靶点的表达水平及表达状态进行定性、定量研究,对筛选优势人群、指导治疗、判断预后具有重大意义。本文简述基于不同分子探针的分子成像技术在肿瘤靶向治疗过程中的应用,对比分析分子成像在靶向治疗中的价值,以期有益于新型治疗策略的开发。     

实体肿瘤免疫相关疗效评价标准的研究进展

[摘要] 近几年,免疫检查点抑制剂疗法飞速发展并取得突破性进展,成为多种晚期肿瘤的首选疗法。但由于其激活抗肿瘤免疫系统的独特作用模式,多种非常规缓解模式相继出现,如延迟反应和假性进展等,给传统疗效评价标准带来挑战,进而促使人们不断探索应对免疫治疗特殊反应的评价指南。本文主要对实体肿瘤多种免疫治疗相关疗效评价标准的探索进程、研究进展及各指南间异同进行系列阐述,并对其目前的挑战和未来发展趋势进行展望。     

肿瘤分子靶向治疗研究现状

分子靶向治疗药物成为近年来肿瘤治疗发展领域的研究热点，以低毒高效的特点逐步成为临床肿瘤治疗的重要部分，大量的临床试验集中于研究该类药物的疗效和毒副反应。本文拟对肿瘤分子靶向治疗药物的最新研究情况加以概述。     

肿瘤乏氧分子靶向治疗

乏氧是多数实体瘤的固有特征之一,可增加肿瘤细胞对放化疗的耐受性、促使肿瘤血管生成,是重要的不良预后因素.靶向杀伤肿瘤内的乏氧细胞成为肿瘤治疗的热点.生物还原性药物可通过特定的还原反应激活为细胞毒性代谢产物进而杀伤乏氧肿瘤细胞,而小分子靶点抑制剂则选择性地作用于乏氧途径中的关键环节,二者为肿瘤的乏氧靶向治疗开辟了新的途径.     

Oxaliplatin: a review in the era of molecularly targeted therapy

Objective

To review preclinical and clinical data for oxaliplatin in the current context of molecularly targeted therapy.

Methods of Study Selection

We searched the PubMed and PubChem databases by combining the search terms “oxaliplatin” or “platinum” or both, with “clinical trials,” “pharmacokinetics,” and “pharmacodynamics.”

Data Extraction and Synthesis

Oxaliplatin has a complicated pharmacokinetic profile, with activity against digestive cancers in particular. It has several mechanisms of action, but cancer cells can develop resistance. Real or potential synergism has been observed when oxaliplatin is combined with other cytotoxic agents or molecularly targeted agents. Peripheral neuropathy is a prominent toxic effect.

Conclusions

Oxaliplatin lends itself to further clinical research in combination with molecularly targeted therapy.     

Advances in immunotherapy and molecular targeted therapy of gestational trophoblastic tumor: current practice and future perspectives

Gestational trophoblastic neoplasia (GTN) is a rare pregnancy-related gynecological malignancy caused by abnormal proliferation of placental trophoblastic cells. It can invade the uterine muscle layer and metastasize early, more common in women of childbearing age. GTN is invasive and can destroy surrounding tissues and blood vessels, causing massive bleeding in uterus and metastatic sites (such as lung, liver, brain, etc.) through blood transfer. Chemotherapy is the main treatment for GTN, and the disease is extremely sensitive to chemotherapy and can be cured by chemotherapy. However, in clinical practice, a large number of patients have failed chemotherapy or even multiple treatments due to drug resistance, recurrence or metastasis of special sites. Therefore, how to individually select the initial chemotherapy regimen and reduce the occurrence of drug resistance is the key to the treatment of high-risk GTN. With the remarkable efficacy of immunotherapy in endometrial cancer, cervical cancer and other diseases, the research on GTN has been further deepened. Therefore, this review discusses the mechanism, methods and efficacy of GTN immunotherapy and molecular targeted therapy, in order to provide new ideas for the diagnosis and treatment of GTN.