Molecular targeted drugs and chimeric antigen receptor (CAR) T cell therapy represent specific biological treatments that have significantly improved the efficacy of treating hematologic malignancies. However, they face challenges such as drug resistance and recurrence after treatment. Combining molecular targeted drugs and CAR-T cells could regulate immunity, improve tumor microenvironment (TME), promote cell apoptosis, and enhance sensitivity to tumor cell killing. This approach might provide a dual coordinated attack on cancer cells, effectively eliminating minimal residual disease and overcoming therapy resistance. Moreover, molecular targeted drugs can directly or indirectly enhance the anti-tumor effect of CAR-T cells by inducing tumor target antigen expression, reversing CAR-T cell exhaustion, and reducing CAR-T cell associated toxic side effects. Therefore, combining molecular targeted drugs with CAR-T cells is a promising and novel tactic for treating hematologic malignancies. In this review article, we focus on analyzing the mechanism of therapy resistance and its reversal of CAR-T cell therapy resistance, as well as the synergistic mechanism, safety, and future challenges in CAR-T cell therapy in combination with molecular targeted drugs. We aim to explore the benefits of this combination therapy for patients with hematologic malignancies and provide a rationale for subsequent clinical studies.

中文翻译：

---

分子靶向药物联合CAR-T细胞治疗血液系统恶性肿瘤的进展


分子靶向药物和嵌合抗原受体（CAR）T细胞疗法代表了特异性生物疗法，显着提高了治疗血液恶性肿瘤的疗效。然而，他们面临着耐药性和治疗后复发等挑战。分子靶向药物与CAR-T细胞相结合，可以调节免疫，改善肿瘤微环境（TME），促进细胞凋亡，增强对肿瘤细胞杀伤的敏感性。这种方法可能对癌细胞提供双重协调攻击，有效消除微小残留疾病并克服治疗耐药性。而且，分子靶向药物可以通过诱导肿瘤靶抗原表达、逆转CAR-T细胞耗竭、减少CAR-T细胞相关毒副作用，直接或间接增强CAR-T细胞的抗肿瘤作用。因此，分子靶向药物与CAR-T细胞相结合是治疗血液恶性肿瘤的一种有前景的新颖策略。在这篇综述文章中，我们重点分析CAR-T细胞治疗耐药的机制及其逆转CAR-T细胞治疗耐药的机制，以及CAR-T细胞治疗与分子靶向药物联合的协同机制、安全性和未来挑战。我们的目的是探索这种联合疗法对血液恶性肿瘤患者的益处，并为后续临床研究提供依据。