胃癌的分子靶向治疗

晚期胃癌患者的治疗主要为全身化疗,但胃癌的化疗总体来讲尚没有一致公认的标准方案,迫切需要新疗法出现。分子靶向治疗以某些标志性分子为靶点,有效干预受该分子调控并与肿瘤发展密切相关的信号通路,是目前肿瘤治疗领域发展的新方向。目前应用分子靶向治疗胃癌主要有以下几种机制。     

胃癌分子靶向治疗的研究进展

目前晚期胃癌的治疗方式是以全身化疗为主的综合治疗。尽管化疗能够延长肿瘤患者的生存期,但副作用较明显,近年来,随着对胃癌的各种相关分子的信号转导通路的逐渐认识,在分子水平抑制肿瘤生长的治疗方式越来越受到人们关注,众多靶向药物应运而生,如曲妥珠单抗、阿帕替尼、Claudin18.2等,各种靶向药物为晚期胃癌的治疗提供了良好的前景。     

乳腺癌分子靶向治疗临床研究进展

乳腺癌是威胁妇女健康的主要恶性肿瘤，化疗和内分泌治疗是乳腺癌主要的全身治疗手段，在复发转移乳腺癌的解救治疗和早期乳腺癌的辅助治疗中取得明确疗效。分子肿瘤学研究成果，义使分子靶向药物在乳腺癌治疗中取得显著疗效。赫赛汀(Herceptin)是针对癌细胞Her-2基因靶点的第一个分子靶向药物，为乳腺癌临床治疗带来了新的突破。     

食管癌分子靶向治疗

与传统细胞毒性化疗相比,分子靶向治疗能更特异地作用于肿瘤而毒性反应较轻.分子靶向治疗是一种全新治疗模式,食管癌的分子靶向治疗的临床研究才刚刚开始.     

晚期原发性肝癌内科治疗进展

摘 要：原发性肝癌是中国发病率和死亡率均较高的恶性肿瘤。目前临床上晚期原发性肝癌的治疗以全身系统性药物治疗为主,主要包括系统化疗、分子靶向治疗以及免疫治疗等。该文就近年来晚期原发性肝癌的内科治疗研究进展作一综述。     

小细胞肺癌的分子靶向治疗现状与展望

小细胞肺癌以侵袭性高、容易出现远处转移而著称,预后极差。化疗是各期小细胞肺癌治疗的基石所在。与化疗相比,分子靶向治疗具有高效、低毒的特点,是目前肿瘤治疗发展的新方向。近年来,一些分子靶向药物在治疗中小细胞肺癌患者治疗中进行了临床研究。本文将对小细胞肺癌分子靶向治疗的重要分子靶点和相应药物进行论述。      

自噬与肺癌化疗和靶向药物耐药关系的研究进展

肺癌是全球癌症相关死因第一位的恶性肿瘤,目前临床上治疗中晚期肺癌主要以化疗和分子靶向治疗为主。肿瘤耐药是临床上化疗和靶向治疗失败的最主要原因之一。自噬相关分子参与机体生理病理众多过程而且调控机制非常复杂。本文主要综述在肺癌化疗和靶向药物耐药的过程中自噬相关分子发生的改变,旨在阐明自噬与肺癌耐药的关系。     

表皮生长因子受体-酪氨酸激酶抑制剂靶向治疗联合全身化疗治疗Ⅳ期肺腺癌的临床疗效

目的 探讨表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKI)靶向治疗联合全身化疗治疗Ⅳ期肺腺癌的临床疗效.方法 根据治疗方案不同将102例肺腺癌患者分为观察组(n=54)和对照组(n=48),对照组患者给予全身化疗,观察组患者在全身化疗的基础上给予EGFR-TKI靶向治疗.比较两组患者的临床疗效、免疫球蛋白[免疫...     

转移性结直肠癌维持治疗的进展

摘 要：目前,转移性结直肠癌（metastatic colorectal cancer,mCRC）的标准一线治疗方案是在化疗药物基础上联合分子靶向药物。对于完成一线治疗且达到完全缓解、部分缓解或稳定的转移性结直肠癌患者,与持续化疗或单纯观察相比,维持治疗不仅可以巩固一线治疗疗效,延缓疾病进展,而且可以减轻化疗药物的蓄积性不良反应,改善患者生存质量,最终达到延长总生存期的目的。维持治疗包括化疗药物、分子靶向药物和化疗药物联合分子靶向药物维持治疗3种方式,近年来已成为转移性结直肠癌研究的重要方向,但仍有许多问题尚待进一步探索和研究。     

部分临床常用药物作为抗肿瘤增效药物的应用与机制

部分临床常用药物虽并不作为抗肿瘤药物应用,却可增进化疗药物和分子靶向药物的疗效,或逆转肿瘤对化疗药物和分子靶向药物的耐药性。对于晚期、多线治疗失败的难治性肿瘤,值得尝试单独应用或与化疗药物、分子靶向药物联用。这些药物包括pH值调节药物、血糖调节药物及心血管类药物等。     

HER-2阳性炎性乳腺癌的靶向治疗进展

原癌基因人类表皮生长因子受体2（HER-2）阳性炎性乳腺癌是指HER-2过表达或扩增的炎性乳腺癌。临床上以乳房表面皮肤呈炎性改变而没有溃疡形成、局部及全身快速进展为特点,表现出更高的侵袭性。尽管炎性乳腺癌预后差,但新辅助化疗、手术及放疗等多学科综合治疗,尤其是分子靶向治疗显著改变了本病的自然进程。本文就近年来HER-2阳性炎性乳腺癌的分子靶向治疗进展作一综述。     

三阴性乳腺癌化疗进展

三阴性乳腺癌作为乳腺癌的一种特殊亚型,对内分泌治疗和现有靶向治疗无效,并且通常复发较早、进展迅速、预后较差。现就三阴性乳腺癌的分子分型及其临床价值、化疗药物和化疗方案以及化疗和潜在的新靶点药物联合方面的最新进展作一综述。     

Combining surgery and chemotherapy for invasive bladder cancer: current and future directions

More than 13,000 patients died from invasive bladder cancer in 2005 alone. Radical cystectomy is the most commonly prescribed treatment for patients with muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease that is refractory to intravesical therapy. Despite advances in surgical technique and improved understanding of the role of pelvic lymphadenectomy, 5-year survival probabilities suggest that improvements in treatment are necessary. The maturation of several randomized clinical trials on perioperative chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an integrated treatment program of systemic chemotherapy and definitive locoregional therapy may improve the outcome for bladder cancer patients. The next frontier is the molecular characterization of this spectrum of diseases that make up invasive bladder cancer and targeted therapeutics. Prospective validation of molecular markers and evaluation of novel therapeutic agents, alone or in combination with established cytotoxic agents, provide hope of better outcomes for bladder cancer patients.     

Combining surgery and chemotherapy for invasive bladder cancer: current and future directions

More than 13,000 patients died from invasive bladder cancer in 2005 alone. Radical cystectomy is the most commonly prescribed treatment for patients with muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease that is refractory to intravesical therapy. Despite advances in surgical technique and improved understanding of the role of pelvic lymphadenectomy, 5-year survival probabilities suggest that improvements in treatment are necessary. The maturation of several randomized clinical trials on perioperative chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an integrated treatment program of systemic chemotherapy and definitive locoregional therapy may improve the outcome for bladder cancer patients. The next frontier is the molecular characterization of this spectrum of diseases that make up invasive bladder cancer and targeted therapeutics. Prospective validation of molecular markers and evaluation of novel therapeutic agents, alone or in combination with established cytotoxic agents, provide hope of better outcomes for bladder cancer patients.     

Traitement systémique des métastases cérébrales de cancer bronchique

Systemic treatment of lung cancer patients with brain metastases is based on clinical (presence of symptomatic intracranial lesions), pathological and molecular characteristics of the disease. The efficacy of standard platinum-based chemotherapy is comparable inside and outside the brain, justifying its use as front-line therapy. The intracranial efficacy of targeted therapies (EGFR tyrosine kinase inhibitors, ALK inhibitors) is demonstrated, and is globally superior to the efficacy of standard chemotherapy, justifying their use as front-line therapy in case of EGFR activating mutation or ALK rearrangement (providing the change in the crizotinib label in France). The concomitant use of whole brain radiotherapy and a systemic treatment (chemotherapy or targeted therapy) is not recommended in the absence of a demonstrated better efficacy and/or acceptable safety profile. Several trials are ongoing to assess new whole brain radiotherapy modalities, new targeted therapies alone or in combination, especially exploring immunotherapy.     

Current treatment and recent progress in gastric cancer

Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.     

Systemic Therapy in the Setting of Central Nervous System (CNS) Metastases in Breast Cancer

Purpose of Review

Over 25% of patients with metastatic breast cancer will develop brain metastases. Recent advances in systemic therapy, especially molecularly targeted agents, have improved control of extracranial disease, but have had limited effect on intracranial disease. In this review, we discuss the barriers and challenges associated with employing systemic therapy to treat brain metastases. We also provide an overview of current systemic therapy used as standard of care in all subtypes of breast cancer that have metastasized to the brain, as well as describe novel agents that are currently under study in preclinical models or clinical trials.

Recent Findings

While there are few systemic therapies that are standard of care for the treatment of breast cancer brain metastases, there are many novel agents currently in development or under active investigation. Detailed genomic analysis has led to a better understanding of the molecular aberrations that drive metastasis in the different subtypes of breast cancer, leading to rational approaches to the development of targeted molecular therapy.

Summary

The most promising systemic therapeutic modalities for treating breast cancer brain metastases utilize targeted molecular agents or molecular exploitation of the blood-brain barrier in combination with cytotoxic chemotherapy to enhance entry into the CNS.

     

Combinational therapy: New hope for pancreatic cancer?

Pancreatic cancer is a devastating disease with a low overall survival rate. Chemotherapy is the most common treatment for patients presenting with advanced pancreatic cancer. Gemcitabine achieves a modest improvement in overall survival and is the gold standard for advanced pancreatic cancer treatment. Capecitabine and S-1, derivatives of 5-fluorouracil (5-FU), offers minimal clinical benefits. Folfirinox represents a new and aggressive regimen that might benefit patients of metastatic pancreatic cancer with good performance status. Other chemotherapy drugs such as platinums and irinotecan do not provide significant improvement in overall survival, but have been used as part of combinational therapies. Comparing to systemically delivered chemotherapy, regional intra-arterial chemotherapy achieves higher local drug concentration in tumors with lower systemic drug toxicity, and may serve as a better treatment regimen. Although there have been progress made in chemotherapeutic strategies against pancreatic cancer, the overall survival is not significantly improved in the last decade. Recently, development of chemotherapy in combination with molecular targeted therapies holds great promise in pancreatic cancer treatment, especially in patients with metastatic disease. Growing bodies of preclinical and clinical evidences indicate that the combination of conventional modalities with specific molecular targeted therapy increase the efficacy of the monotherapy without an increase in toxicity. In this review, we summarized the current regimens of chemotherapy and molecular targeted therapy for advanced pancreatic cancer and highlighted the novel combinational treatments tested in recent clinical trials.     

Systemic therapy in the management of metastatic or advanced salivary gland cancers

ABSTRACT: Salivary gland cancers are very rare tumors. They are characterized by a histologic heterogeneity and a poor outcome. According to this rarity, few prospective data are available to date. No standard recommendations could be held for the use of systemic therapy in these tumors. Several case reports and small studies have investigated the contribution of different agents of chemotherapy. With the extension of molecular biology approach in oncology several signaling pathways have been discovered in different cancers including salivary gland cancers; thus a number of targeted therapies have been investigated. This paper reviewed exhaustively the studies investigating the role of systemic therapies (chemotherapy, targeted therapy, hormone therapy) in salivary gland cancers.     

Current status of molecularly targeted therapy for hepatocellular carcinoma: basic science

Conventional systemic chemotherapy has been developed with so-called anti-cancer agents, essentially screened for cytotoxicity to cultured cancer cells. However, in patients with hepatocellular carcinoma (HCC), the role of chemotherapy is quite limited because most anti-cancer agents are ineffective and relatively toxic to HCC patients with chronic liver diseases. On the other hand, accumulated understanding of the molecular mechanisms regulating cancer progression has led to novel development of molecularly targeted therapies with cytostatic agents. Recently, a phase III clinical trial revealed a multi-kinase inhibitor, Sorafenib, as the first agent leading to improved overall survival of patients with advanced HCC. A new era of HCC treatment has arrived, based on identification of deranged signaling pathways of cancer cells or their microenvironment. This review summarizes the molecular hallmarks of HCC with a focus on angiogenesis, growth signals, and mitotic stress, and a novel concept “synthetic lethality” for the targeted therapy strategy.