下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Targeted therapy and immunotherapy for gastric cancer: rational strategies, novel advancements, challenges, and future perspectives.
胃癌(GC)是全球最常见的恶性肿瘤之一,其治疗一直是医学研究的重点。
胃癌(GC)是全球最常见的恶性肿瘤之一,其治疗一直是医学研究的焦点。本文系统综述了胃癌靶向治疗和免疫治疗的现状与进展,这两种治疗策略近年来已成为具有巨大潜力的重要治疗手段,并总结了此类治疗的疗效与安全性。针对胃癌关键靶点的靶向治疗,包括表皮生长因子受体(EGFR)、人表皮生长因子受体2(HER2)和血管内皮生长因子(VEGF)/VEGF受体(VEGFR),通过抑制肿瘤进展和/或血供已显示出显著的疗效。特别是针对HER2阳性胃癌患者的HER2靶向药物已取得显著突破。为解决HER2靶向药物的原发性和获得性耐药问题,已开发出新型治疗药物,包括双特异性抗体和靶向HER2的抗体药物偶联物(ADC)。免疫治疗通过激活机体抗肿瘤免疫系统增强对癌细胞的识别和清除。程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡配体1(PD-L1)抗体是最常用的免疫治疗药物,已在胃癌治疗中取得一定成功。创新性免疫治疗模式,包括过继性免疫细胞治疗、肿瘤疫苗、非特异性免疫调节剂治疗和溶瘤病毒,在胃癌早期临床试验中已显示出前景。临床试验已支持靶向治疗和免疫治疗可显著改善胃癌患者的生存期和生活质量。然而,随着肿瘤免疫微环境研究的进展,此类疗法的效果需要进一步改善并更加个性化。仍需进一步研究以解决胃癌此类疗法的耐药性和不良事件问题。应进一步探索此类疗法与个体化治疗策略的联合应用,并开发新药,为胃癌患者提供更有效的治疗。
Gastric cancer (GC) is one of the most common malignant tumors worldwide, and its treatment has been a focus of medical research. Herein we systematically review the current status of and advancements in targeted therapy and immunotherapy for GC, which have emerged as important treatment strategies in recent years with great potential, and summarize the efficacy and safety of such treatments. Targeted therapies against key targets in GC, including epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR), have shown remarkable therapeutic efficacies by inhibiting tumor progression and/or blood supply. In particular, markable breakthroughs have been made in HER2-targeting drugs for HER2-positive GC patients. To address intrinsic and acquired resistances to HER2-targeting drugs, novel therapeutic agents including bispecific antibodies and antibody-drug conjugates (ADC) targeting HER2 have been developed. Immunotherapy enhances the recognition and elimination of cancer cells by activating body anticancer immune system. Programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antibodies are the most commonly used immunotherapeutic agents and have been used with some success in GC treatment. Innovative immunotherapy modalities, including adoptive immune cell therapy, tumor vaccines, and non-specific immunomodulators therapy, and oncolytic viruses have shown promise in early-stage clinical trials for GC. Clinical trials have supported that targeted therapy and immunotherapy can significantly improve the survival and quality of life of GC patients. However, the effects of such therapies need to be further improved and more personalized, with advancement in researches on tumor immune microenvironment. Further studies remain needed to address the issues of drug resistance and adverse events pertaining to such therapies for GC. The combined application of such therapies and individualized treatment strategies should be further explored with novel drugs developed, to provide more effective treatments for GC patients.
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