Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Int J Mol Sci. 2023 Sep 6;24(18):13726. doi: 10.3390/ijms241813726.
Antibody drug conjugates (ADCs) are novel medications that combine monoclonal antibodies with cytotoxic payloads, enabling the selective delivery of potent drugs to cancer cells expressing specific surface antigens. This targeted strategy seeks to optimize treatment effectiveness while reducing the risk of systemic toxicity, distinguishing ADCs from conventional chemotherapy. The rapid growth in ADC research has led to numerous developments and approvals for cancer treatment, with significant impacts on the management of breast cancer. ADCs like T-DXd for HER2-low disease and sacituzumab govitecan for triple negative breast cancer (TNBC) have provided valuable options for challenging subtypes of breast cancer. However, essential questions still need to be addressed, including the optimal order of ADCs amidst the growing number of newly developed ones and strategies to overcome resistance mechanisms. Preclinical studies have shed light on potential resistance mechanisms, emphasizing the potential benefit of combinational approaches with other agents such as immune checkpoint inhibitors (ICIs) and targeted tyrosine kinase inhibitors (TKIs) to enhance treatment effectiveness. Additionally, personalized approaches based on molecular profiling hold promise in tailoring ADC treatments to individual tumors, identifying unique molecular markers for each patient to optimize treatment efficacy while minimizing side effects.
抗体药物偶联物(ADCs)是一种新型药物,将单克隆抗体与细胞毒性有效载荷结合在一起,使强效药物能够选择性地递送至表达特定表面抗原的癌细胞。这种靶向策略旨在优化治疗效果,同时降低全身性毒性的风险,使 ADC 有别于传统化疗。ADC 研究的快速发展带来了许多癌症治疗的进展和批准,对乳腺癌的治疗管理产生了重大影响。针对 HER2 低表达疾病的 T-DXd 和用于三阴性乳腺癌(TNBC)的 sacituzumab govitecan 等 ADC 为具有挑战性的乳腺癌亚型提供了有价值的选择。然而,仍有一些重要问题需要解决,包括在越来越多新开发的 ADC 中,ADC 的最佳使用顺序以及克服耐药机制的策略。临床前研究揭示了潜在的耐药机制,强调了与其他药物(如免疫检查点抑制剂[ICIs]和靶向酪氨酸激酶抑制剂[TKIs])联合使用的组合方法的潜在益处,以增强治疗效果。此外,基于分子谱的个性化方法有望为每个患者确定独特的分子标志物,从而优化治疗效果,同时最小化副作用,为 ADC 治疗量身定制。