Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications.
Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications.
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DOI：
10.1158/1078-0432.ccr-19-2300
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发表时间：
2020-11-01
期刊：
影响因子：
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通讯作者：
Zhao JJ
中科院分区：
文献类型：
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作者：
Bergholz JS;Wang Q;Kabraji S;Zhao JJ
小分子靶向治疗已在临床上显示出突出的潜力。这些药物旨在通过选择性地攻击癌细胞，同时对正常细胞造成最小的损害来尽量减少不良反应。虽然对靶向治疗的初始反应可能很高，产生积极的反应率，并经常改善很大比例的患者的生存率，但耐药性往往限制了长期有效性。另一方面，免疫疗法已经证明了持久的结果，但对于有限数量的患者。越来越多的证据表明，一些靶向药物可以调节抗肿瘤免疫应答的不同组分。这些包括通过抑制肿瘤细胞内在免疫逃避程序或增强抗原性的免疫致敏，以及对免疫效应细胞和免疫抑制细胞的直接作用。因此，这两种方法的结合有可能为患者带来协同和持久的结果。本文就小分子靶向抑制剂与免疫治疗结合的最新进展作一综述。特别是，我们讨论了特定的致癌事件如何差异影响免疫反应，以及这些发现对免疫治疗和靶向治疗有效组合的合理设计的影响。
Small molecule targeted therapies have demonstrated outstanding potential in the clinic. These drugs are designed to minimize adverse effects by selectively attacking cancer cells while exerting minimal damage to normal cells. Although initial response to targeted therapies may be high, yielding positive response rates and often improving survival for an important percentage of patients, resistance often limits long-term effectiveness. On the other hand, immunotherapy has demonstrated durable results, yet for a limited number of patients. Growing evidence indicates that some targeted agents can modulate different components of the anti-tumor immune response. These include immune sensitization by inhibiting tumor cell-intrinsic immune evasion programs or enhancing antigenicity, as well as direct effects on immune effector and immunosuppressive cells. The combination of these two approaches, therefore, has the potential to result in synergistic and durable outcomes for patients. In this review, we focus on the latest advances on integrating immunotherapy with small molecule targeted inhibitors. In particular, we discuss how specific oncogenic events differentially affect immune response, and the implications of these findings on the rational design of effective combinations of immunotherapy and targeted therapies.