Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, 30322, USA.
Front Med. 2022 Oct;16(5):701-713. doi: 10.1007/s11684-022-0951-0. Epub 2022 Sep 24.
A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.
在肺癌治疗中，一个显著的临床挑战是管理第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（EGFR-TKIs）的获得性耐药，如奥希替尼，它在治疗具有 EGFR 激活突变的晚期 NSCLC 方面取得了显著成功，以实现最大的反应持续时间或治疗缓解。细胞凋亡是一种与癌症发展和治疗密切相关的主要程序性细胞死亡类型。逃避细胞凋亡被认为是癌症的一个关键标志，因此，获得细胞凋亡抵抗是癌症治疗中药物获得性耐药的一个关键机制。已经清楚地表明，有效诱导细胞凋亡是第三代 EGFR-TKIs（特别是奥希替尼）发挥治疗效果的关键机制，而对细胞凋亡的耐药性与获得性耐药的出现密切相关。因此，使用各种方法恢复细胞对凋亡的敏感性有望成为管理第三代 EGFR-TKIs 获得性耐药的有效策略。
