The Affiliated Hospital of Qingdao University, Qingdao, 266071, People's Republic of China.
Qingdao Cancer Institute, Qingdao University, Qingdao, 266071, People's Republic of China.
Int J Nanomedicine. 2024 May 1;19:3919-3942. doi: 10.2147/IJN.S453265. eCollection 2024.
Typical physiological characteristics of tumors, such as weak acidity, low oxygen content, and upregulation of certain enzymes in the tumor microenvironment (TME), provide survival advantages when exposed to targeted attacks by drugs and responsive nanomedicines. Consequently, cancer treatment has significantly progressed in recent years. However, the evolution and adaptation of tumor characteristics still pose many challenges for current treatment methods. Therefore, efficient and precise cancer treatments require an understanding of the heterogeneity degree of various factors in cancer cells during tumor evolution to exploit the typical TME characteristics and manage the mutation process. The highly heterogeneous tumor and infiltrating stromal cells, immune cells, and extracellular components collectively form a unique TME, which plays a crucial role in tumor malignancy, including proliferation, invasion, metastasis, and immune escape. Therefore, the development of new treatment methods that can adapt to the evolutionary characteristics of tumors has become an intense focus in current cancer treatment research. This paper explores the latest understanding of cancer evolution, focusing on how tumors use new antigens to shape their "new faces"; how immune system cells, such as cytotoxic T cells, regulatory T cells, macrophages, and natural killer cells, help tumors become "invisible", that is, immune escape; whether the diverse cancer-associated fibroblasts provide support and coordination for tumors; and whether it is possible to attack tumors in reverse. This paper discusses the limitations of targeted therapy driven by tumor evolution factors and explores future strategies and the potential of intelligent nanomedicines, including the systematic coordination of tumor evolution factors and adaptive methods, to meet this therapeutic challenge.
肿瘤的典型生理特征，如弱酸性、低氧含量以及肿瘤微环境（TME）中某些酶的上调，使它们在受到药物和响应性纳米药物的靶向攻击时具有生存优势。因此，近年来癌症治疗取得了显著进展。然而，肿瘤特征的进化和适应仍然给当前的治疗方法带来了许多挑战。因此，高效和精准的癌症治疗需要了解肿瘤进化过程中癌细胞中各种因素的异质性程度，以利用典型的 TME 特征并管理突变过程。高度异质的肿瘤和浸润性基质细胞、免疫细胞和细胞外成分共同构成了独特的 TME，它在肿瘤恶性行为中起着至关重要的作用，包括增殖、侵袭、转移和免疫逃逸。因此，开发能够适应肿瘤进化特征的新治疗方法已成为当前癌症治疗研究的重点。本文探讨了癌症进化的最新认识，重点关注肿瘤如何利用新抗原塑造其“新面貌”；细胞毒性 T 细胞、调节性 T 细胞、巨噬细胞和自然杀伤细胞等免疫系统细胞如何帮助肿瘤变得“不可见”，即免疫逃逸；多样化的癌症相关成纤维细胞是否为肿瘤提供支持和协调；以及是否有可能逆转攻击肿瘤。本文讨论了受肿瘤进化因素驱动的靶向治疗的局限性，并探讨了未来的策略和智能纳米药物的潜力，包括肿瘤进化因素的系统协调和自适应方法，以应对这一治疗挑战。
