前列腺癌骨转移相关疼痛的治疗

前列腺癌是容易发生骨转移的恶性肿瘤之一,包括癌细胞、成骨细胞、破骨细胞和骨基质细胞及一系列生长因子在内的多种因素参与了骨转移.骨转移癌形成后,局部病理生理变化、高钙血症、病理性骨折和中枢神经系统致敏等因素对疼痛的发生和持续起重要作用.以吗啡为代表的强阿片类药加以其他必要辅助药物能使大多数患者癌痛获得满意缓解.而外照射放疗（external beam radiotherapy,EBRT）可缓解骨转移瘤引起的疼痛,减少或消除镇痛药的使用,减少病理性骨折的发生,同时对减轻肿瘤对脊髓的压迫等有明显的疗效.对有症状的转移性激素抵抗性前列腺癌患者而言放射性核素治疗可有效控制骨转移相关疼痛.在减少前列腺癌骨转移的骨相关事件方面,Denosumab优于唑来膦酸,而一些研发中的新的靶向药物或许能在未来更好地控制前列腺癌骨转移相关疼痛.     

恶性肿瘤骨转移靶向治疗及免疫治疗进展

恶性肿瘤的骨转移严重威胁癌症患者的生活质量与生存获益,而放疗等传统抗肿瘤治疗手段对于骨转移灶的疗效不够理想,仅能起到对于局部病灶的控制作用。近年来,双膦酸盐类药物及地诺单抗等靶向药物有效降低了骨相关不良事件的发生率,并且对于部分癌种提高了骨转移患者的生存获益。随着肿瘤免疫疗法的突破,探索免疫检查点阻断和其他潜在骨转移灶免疫治疗靶点的应用价值给骨转移患者的治疗带来新的希望。本文重点针对恶性肿瘤骨转移的靶向治疗及免疫治疗进展进行综述。      

骨转移癌分子靶向治疗进展

常见恶性肿瘤患者不但骨转移的发生率较高,而且骨相关事件（skeletal related events,SRE）也频繁出现,严重影响着患者的生活质量。双膦酸盐是肺癌骨转移全身治疗的基础用药,能将首次发生骨相关事件的中位时间平均延迟2～3个月,但患者的肾功能状况及不良反应限制了其在临床中的应用。随着骨转移癌机制研究的深入,越来越多的临床前或临床研究验证了靶向药物如地诺单抗等在延迟乳腺癌、前列腺癌、多发性骨髓瘤和其他实体肿瘤骨转移癌所致骨相关事件的发生方面优效于双膦酸盐。     

宫颈癌骨转移的研究进展

宫颈癌是最常见的女性生殖道恶性肿瘤.骨骼是宫颈癌少见的转移部位,一旦发生骨转移,常预示患者的生活质量下降和生存期缩短.针对骨转移采取多学科综合治疗模式制定个体化治疗,能有助于提高疾病控制率并延长患者的生存期.本文首先将介绍宫颈癌骨转移的临床特征和诊断要点,然后重点综述手术、放疗、化疗、靶向及免疫治疗、骨改良药物治疗及止...     

骨转移癌微环境与治疗靶点

目前骨转移癌的治疗手段相当有限,且疗效不显著.骨转移癌靶向治疗研究是当前的热点,同时也是难点.对骨微环境中成骨细胞、破骨细胞及肿瘤细胞等相互关系的最新研究成果,可为临床上治疗骨转移癌提供新的思路和方法.     

《中国肿瘤临床》文章推荐:恶性肿瘤骨转移靶向治疗及免疫治疗进展

恶性肿瘤的骨转移严重威胁癌症患者的生活质量与生存获益,而放疗等传统抗肿瘤治疗手段对于骨转移灶的疗效不够理想,仅能起到对于局部病灶的控制作用。近年来,双膦酸盐类药物及地诺单抗等靶向药物有效降低了骨相关不良事件的发生率,并且对于部分癌种提高了骨转移患者的生存获益。随着肿瘤免疫疗法的突破,探索免疫检查点阻断和其他潜在骨转移灶免疫治疗靶点的应用价值给骨转移患者的治疗带来新的希望。     

肾细胞癌治疗药物的研发进展

肾细胞癌(renal cell carcinoma, RCC)是一种致命的恶性肿瘤,其治疗方式包括手术切除、靶向治疗、免疫治疗和联合治疗等。近年来,随着分子生物学和药物研发技术的不断发展,肾细胞癌的药物治疗取得了长足的进展,包括靶向治疗药物的不断更新、免疫治疗的革命性突破以及联合治疗的策略优化。该文将对肾细胞癌的靶向治疗、免疫治疗以及联合治疗进行系统综述。     

镇痛药联合双膦酸盐治疗恶性肿瘤骨转移的相关 进展

骨转移是晚期恶性肿瘤最常见的并发症之一。最常见的发生骨转移的恶性肿瘤,主要包括肺癌、乳腺癌、前列腺癌、 肾癌、胃肠道肿瘤等。晚期肿瘤一旦发生骨转移,会引起局部的骨质破坏,从而引起骨痛、病理性骨折、神经压迫、高钙血症等 一系列骨相关事件（SREs）,严重影响患者的生活质量,甚至导致患者脊髓压迫,引起截瘫。晚期恶性肿瘤骨转移的患者大多 已经失去了手术的机会,针对骨转移瘤引起的相关并发症治疗,除了积极对原发肿瘤进行病因治疗外,骨转移性癌痛应遵循全 身药物治疗和局部治疗相结合的模式,局部治疗包括介入治疗和姑息性放疗。而全身药物治疗包括非甾体类药物、弱阿片类 药物、阿片类药物、双膦酸盐/地舒单抗、抗抑郁药、抗惊厥药及抗癫痫药、中成类药物等联合应用。通过综合治疗缓解患者的 疼痛症状,预防骨相关不良事件的发生,降低治疗不良反应,提高生存质量,更重要的是改善了生存预后。本文就镇痛药联合 双膦酸盐治疗晚期肿瘤骨转移的进展进     

实体瘤骨转移靶向治疗进展

多种实体瘤如乳腺癌、前列腺癌等在远处转移时具有明显的趋骨性.骨转移可严重影响患者的生活质量,并间接影响患者的生存.目前二磷酸盐和地诺单抗是骨转移的标准治疗药物,但总体治疗效果有限.随着骨转移分子机制研究的进展,近年出现了多种新兴靶向治疗药物.本文旨在根据靶向目标及机制的不同,对已在实体瘤骨转移中开展临床研究和试验的靶向治疗进展作一概述.     

唑来膦酸联合放疗治疗恶性肿瘤骨转移疗效分析

骨骼是恶性肿瘤发生转移的好发部位,30%～70%的恶性肿瘤会发生骨转移,骨转移癌常见的并发症有骨痛、病理性骨折、骨髓压迫以及恶性肿瘤引起的高钙血症(HCM)[1]等,严重影响患者的生存质量.自2005年1月至2007年2月我们将放射治疗和唑来膦酸联合使用治疗骨转移取得了较满意疗效,现报道如下.     

前列腺癌骨转移机制及新型靶向治疗的最新研究进展

前列腺癌是唯一最先发生骨转移而非内脏转移的实体肿瘤,骨转移在临床上十分常见,不仅降低了患者总生存期和生活质量还增加了治疗负担。目前二磷酸盐和地诺单抗是骨转移的标准治疗药物,但总体治疗效果有限。近年来随着对骨转移分子机制的进一步研究,出现了许多骨靶向治疗的新药。本文就其骨转移的“恶性循环”机制及针对骨转移潜在作用靶点开展临床研究和试验的骨靶向药物进展作一综述。     

Molecular treatment strategies and surgical reconstruction for metastatic bone diseases

Molecular mechanism of bone metastasis development is extremely complex. It is determined by intrinsic properties of cancer cells or cancer stem cells (CSCs) and intricate bone microenvironment. Therefore, molecular treatment strategies have been suggested to directly induce cancer cells apoptosis and to target vascular and bone microenvironment as well, thus inhibiting vicious cycles established between osteoblasts/osteoclasts and metastatic cancer cells. Chemokine/chemokine receptor pathway, adhesion molecules, and proteinases are crucial for bone metastatic process, including migration, adhesion and invasion into bone, angiogenesis and cell proliferation, which could provide potential targets for prevention and treatment of bone metastasis. Restoration of metastasis suppressor genes and microRNAs inhibits bone metastasis. Furthermore, targeting the bone marrow endothelium around cancer cells by use of both antiangiogenic inhibitors and vascular disrupting agents is another promising and valid therapeutic approach. On the other hand, many antitumor drugs/small molecules are limited in reaching tumor site due to a very complex vasculature. Nanotechnology aids in the targeted delivery of antitumor drugs/small molecules. For severe bone lesion, multifunctional implants integrating with antitumor drugs/small molecules and bone forming factors could be effective to reconstruct bone defects and to improve the quality of life in patients with bone metastasis.     

Molecular-target drug

Cancer metastasis involves the complicated steps of tumor growth, angiogenesis, invasion and adhesion. At present new drugs targeting particular molecule (s) responsible for such cancer progression and metastasis have been developed in clinics. Major endpoints for cancer treatment should be prolongation of survival and maintenance of QOL. However, clinical development of such molecular-target based drugs is associated with difficulties in evaluating the efficacy in phase I/II studies prior to entering phase III study, because many of the targeted drugs seem cytostatic rather than cytocidal to tumors. New approaches incorporating technologies of genomics and proteomics may provide an expanding repertoire of molecular targeted therapeutics for clinical evaluation. In this review, the significance and problems of biomarkers available for clinical evaluation of molecular targeted drugs are discussed.     

肝癌靶向治疗的研究进展

随着分子靶向药物的研发和临床应用,肿瘤的分子靶向治疗已成为肿瘤内科的研究热点。现有的研究结果已表明,肿瘤分子靶向治疗具有较好的安全性和有效性,尤其以多靶点Raf激酶抑制剂,表皮生长因子受体（EGFR）和血管内皮生长因子受体（VEGF）为靶点的治疗药物,已在临床中取得较好的疗效。本文就这几种治疗中具有代表性的药物进行综述,并提出今后的分子靶向治疗可能发展的方向。     

Malignant Pleural Mesothelioma: Medical Treatment Update

Malignant pleural mesothelioma (MPM) is a disease usually unaffected by current therapeutic strategies, but for the majority of patients, the use of systemic chemotherapeutic drugs remains the only therapeutic option available. During the past 15-20 years, many phase II and a few phase III clinical trials have studied a large variety of drugs such as anthracyclines, alkylating agents, platinum compounds, taxanes, vinka alkaloids, and antifolates as single agents and in combination, with the aim to increase responses and survival. The combination of pemetrexed and cisplatin tested in the largest phase III randomized trial of malignant pleural mesothelioma ever conducted has become the current standard of care. New targeted therapeutic approaches with a variety of anti–growth factor drugs are currently undergoing investigation worldwide.     

Recent advances in bone-targeted therapies of metastatic prostate cancer

Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved.     

Treatment and prognosis in colorectal cancer patients with bone metastasis.

We have reviewed the cases of every patient presenting with bone metastasis after colorectal surgery and tried to establish the features of this clinical entity and generate basic strategies to the therapeutic management of this condition. Of 928 primary tumor resected colorectal cancer patients, 12 (1.3%) were identified with bone metastasis and included in this study. The majority of primary tumors were located at the rectosigmoid portion of the colon. All cases were highly advanced at the time of diagnosis, including 8 cases of stage IV by TNM classification. Sites of metastatic tumors were concentrated in lumber or pelvic bones. At the onset of bone metastasis, 9 of the 12 cases had other metastatic sites, i.e., only 3 patients had bone metastasis alone. Survival after onset of bone metastasis was very poor, with a median survival of approximately 5 months and a 20% survival rate at 1 year. With regard to cause of death, seven patients died of pulmonary failure, one of liver failure, and one of DIC. Only 2 cases of solitary osseous metastasis have survived more than 1 year. In order to significantly improve prognosis, the early detection of bone metastases is important.     

PI3K抑制剂在乳腺癌治疗中的应用现状

PI3K/Akt/mTOR信号通路是细胞内的重要信号通路,在调节肿瘤细胞的增殖、分化、转移过程中发挥重要作用。该信号通路的激活与多种肿瘤的发生和发展有密切关系。随着近些年对分子生物学的深入研究发现,磷脂酰肌醇3 激酶(PI3K)通路的异常激活在乳腺癌中最为常见,也使得该通路成为乳腺癌新的治疗靶点,现已研发出多种作用于PAM通路各位点蛋白的靶向药物。文章阐述靶向PI3K/AKT/mTOR信号的原理和PI3K抑制剂在乳腺癌治疗中的应用现状,为乳腺癌的个体化治疗提供理论依据。     

Mechanism of tumor synthetic lethal-related targets

Synthetic lethality is becoming more and more important in the precise treatment of oncology. Malignant tumors caused by gene mutations involve a complex DNA signaling process, and inhibition of DNA signaling in different ways may more effectively control the occurrence and development of tumors. Inhibition of tumor paired lethal genes effectively kills tumor cells, and more and more novel drugs that inhibit tumors are developing in this direction. This article reviews the synthetic lethal theory and discusses selection of drugs to target mutated genes in common solid tumors. The synthetic lethal gene pairs, representative targeted drugs, and related characteristics of four tumor types: lung cancer, breast cancer, colon cancer and prostate cancer, are systematically reviewed.     

Current topics in the diagnosis and treatment of malignant fibrous histiocytoma

Malignant fibrous histiocytoma (MFH) is a tumor about which much remains unknown. The cell origin, molecular mechanism of pleomophism and mechanism of pleomorphic change in a cell undergoing malignant change have not been elucidated. MFH-like histological changes are observed in many bone and cartilage sarcomas, and some renal cell carcinomas and malignant lymphomas. These changes occur in many subtypes of sarcomas such as osteogenic sarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and liposarcoma. MFH has been regarded as one tumor classification from its special histopathological features. In clinical pathological studies these tumors are divided into low-grade fibrous tumors and fibrous histiocytic tumors. With the establishment of molecular biological diagnostic methods, MFH-like histological features can be seen in changes in cellular differentiation of many sarcomas. Patients with MFH often have repeated recurrences before a diagnosis is made, and the tumor is partially resected. Furthermore, distance metastasis develops and the prognosis is poor. The sensitivity of MFH to radiotherapy and chemotherapy is insufficient, and evidence is lacking for adjuvant treatment. Rescue following initial treatment failure is extremely difficult. Local control of 70% to 90% can be achieved if a correct diagnosis is made, and a curative wide resection or salvage wide resection are done early. For treatment of bone and soft tissue sarcoma, a correct diagnosis and initial treatment are extremely important. MFHs are rare tumors that occur in every part of the body. Many cases need to be accumulated in joint clinical studies across fields according to organ and specialty, and effective treatment method developed. We need to advance the standardization of treatment for MFH, and eliminate wrong initial treatment through the active provision of information.