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Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

机译：分子靶向治疗的未来癌症治疗：挑战和策略

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摘要

A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.
机译：在过去的十年中，已经出现了一种基于分子靶标的癌症治疗新策略，这些分子靶标不太可能是机体所有细胞所必需的，因此比传统的细胞毒性药物具有更大的治疗窗口，其作用机理是抑制必需的细胞功能。癌症的异常异质性和适应性在肿瘤药物发现方面提出了重大挑战，而复杂肿瘤生物学的概念已引领了开发许多抗癌疗法的框架。蛋白激酶是肿瘤药物开发中最追求的目标。迄今为止，美国食品和药物管理局已经批准了12种小分子激酶抑制剂，还有更多的药物正在临床开发中。随着硼替佐米的临床疗效的证明，泛素蛋白酶体和泛素样蛋白偶联系统也正在成为癌症治疗中的新治疗靶标。在这篇综述中，讨论了使用激酶和蛋白酶体系统抑制剂的靶向癌症治疗策略。还讨论了克服癌症耐药性并通过每种单独药物的加和或协同作用获得更大治疗益处的联合癌症疗法。最后，解决了分子靶向抗癌疗法在未来癌症疗法中的机遇。

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