The concept of post-therapy metastatic spread, cancer repopulation and acquired tumor cell resistance (M-CRAC) rationalizes tumor progression because of tumor cell heterogeneity arising from post-therapy genetic damage and subsequent tissue repair mechanisms. Therapeutic strategies designed to specifically address M-CRAC involve tissue editing approaches, such as low-dose metronomic chemotherapy and the use of transcriptional modulators with or without targeted therapies. Notably, tumor tissue editing holds the potential to treat patients, who are refractory to or relapsing (r/r) after conventional chemotherapy, which is usually based on administering a maximum tolerable dose of a cytostatic drugs. Clinical trials enrolling patients with r/r malignancies, e.g., non-small cell lung cancer, Hodgkin’s lymphoma, Langerhans cell histiocytosis and acute myelocytic leukemia, indicate that tissue editing approaches could yield tangible clinical benefit. In contrast to conventional chemotherapy or state-of-the-art precision medicine, tissue editing employs a multi-pronged approach targeting important drivers of M-CRAC across various tumor entities, thereby, simultaneously engaging tumor cell differentiation, immunomodulation, and inflammation control. In this review, we highlight the M-CRAC concept as a major factor in resistance to conventional cancer therapies and discusses tissue editing as a potential treatment.
治疗后转移扩散、癌症再增殖及获得性肿瘤细胞耐药（M-CRAC）这一概念，将肿瘤进展归因于治疗后遗传损伤及后续组织修复机制所产生的肿瘤细胞异质性。针对M-CRC设计的治疗策略涉及组织编辑疗法，例如低剂量节拍化疗以及联用或不联用靶向治疗的转录调节剂。值得注意的是，传统化疗通常基于细胞抑制药物的最大耐受剂量给药，而肿瘤组织编辑疗法有望治疗对传统化疗耐药或复发（r/r）的患者。针对r/r恶性肿瘤（如非小细胞肺癌、霍奇金淋巴瘤、朗格汉斯细胞组织细胞增生症和急性髓系白血病）患者的临床试验表明，组织编辑疗法可带来切实的临床获益。与传统化疗或前沿精准医疗不同，组织编辑采用多管齐下的策略，针对不同肿瘤实体中M-CRAC的重要驱动因素，同时促进肿瘤细胞分化、免疫调节和炎症控制。本综述重点阐述M-CRAC概念作为传统癌症疗法耐药的主要因素，并探讨组织编辑作为一种潜在治疗方法。
肿瘤(癌症)患者之家