Gene therapy for brain cancer: combination therapies provide enhanced efficacy and safety.
Gene therapy for brain cancer: combination therapies provide enhanced efficacy and safety.
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DOI：
10.2174/156652309789753301
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发表时间：
2009-10
影响因子：
3.6
通讯作者：
Castro MG
中科院分区：
文献类型：
--
作者：
Candolfi M;Kroeger KM;Muhammad AK;Yagiz K;Farrokhi C;Pechnick RN;Lowenstein PR;Castro MG
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑癌。尽管在治疗和深入研究方面取得了重大进展，但GBM患者的预后仍然很差。GBM的治疗挑战包括其侵袭性，肿瘤与重要脑结构的接近通常阻止全切除，以及复发性GBM对常规放疗和化疗的抗性。基因治疗已被提出作为一种有用的辅助GBM，与目前的治疗结合使用。我们实验室的工作表明，条件性细胞毒性与免疫治疗方法的组合用于治疗GBM，在GBM的同系啮齿动物模型中促进大颅内肿瘤肿块的消退和抗肿瘤免疫记忆。本文综述了近年来国内外研究GBM的动物模型，包括啮齿类动物移植模型、内源性啮齿类动物肿瘤模型和犬自发性GBM模型。我们讨论了评估肿瘤进展和治疗效果的非侵入性替代终点，如行为测试和循环生物标志物。越来越多的临床前和临床数据与细胞毒性抗癌治疗会导致免疫抑制的旧教条相矛盾，这种免疫抑制会损害免疫系统产生抗肿瘤反应的能力。审查的结果的影响表明，细胞毒性治疗与免疫治疗的组合将导致协同抗肿瘤疗效与降低神经毒性，并支持临床实施联合细胞毒性-免疫策略治疗GBM患者。
Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults. Despite significant advances in treatment and intensive research, the prognosis for patients with GBM remains poor. Therapeutic challenges for GBM include its invasive nature, the proximity of the tumor to vital brain structures often preventing total resection, and the resistance of recurrent GBM to conventional radiotherapy and chemotherapy. Gene therapy has been proposed as a useful adjuvant for GBM, to be used in conjunction with current treatment. Work from our laboratory has shown that combination of conditional cytotoxic with immunotherapeutic approaches for the treatment of GBM elicits regression of large intracranial tumor masses and anti-tumor immunological memory in syngeneic rodent models of GBM. In this review we examined the currently available animal models for GBM, including rodent transplantable models, endogenous rodent tumor models and spontaneous GBM in dogs. We discuss non-invasive surrogate end points to assess tumor progression and therapeutic efficacy, such as behavioral tests and circulating biomarkers. Growing preclinical and clinical data contradict the old dogma that cytotoxic anti-cancer therapy would lead to an immune-suppression that would impair the ability of the immune system to mount an anti-tumor response. The implications of the findings reviewed indicate that combination of cytotoxic therapy with immunotherapy will lead to synergistic antitumor efficacy with reduced neurotoxicity and supports the clinical implementation of combined cytotoxic-immunotherapeutic strategies for the treatment of patients with GBM.
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