肿瘤微环境介导获得性耐药的研究进展

Research Advance on Role of Tumor Microenvironment in Mediating Acquired Drug Resistance

临床上肿瘤耐药的发生仍然是影响肿瘤疗效的主要因素之一。近二十年来,通过研究传统的单细胞耐药模型使我们对耐药机制有了一定的认识。这些耐药模型在解释肿瘤耐药机制中起着关键性的作用,并且它们在某些情况下可以帮助确定化疗药物的作用靶点。但是,这些模型不能解释肿瘤获得性耐药的机制。因此,为了提高肿瘤化疗的效果,寻找和辨识肿瘤获得性耐药机制已成为当今研究的热点。目前,大量研究认为肿瘤微环境在介导肿瘤获得性耐药和抵抗细胞死亡的生理性调节中发挥了重要作用。肿瘤微环境中特殊的生态位可能为肿瘤细胞亚群提供了一个"避难所",即在最初暴露于化疗药物之后提供了一种生存优势,它促进了肿瘤获得性耐药的发生。本文就肿瘤微环境及其在介导获得性耐药和凋亡抵抗中的作用作一综述。

The emergence of clinical drug resistance continues to be an obstacle for the successful treatment of cancer. In the past twenty years, our primary understanding of the mechanisms associated with drug resistance has been ascertained through investigating unicellular drug-resistant models. These models are critical in elucidating drug-resistant mechanism and have aided in the identification of drug targets in some cases. However, these models do not address resistance mechanisms that contribute to acquired drug resistance. Therefore, to improve the efficacy of cancer chemotherapy, seeking and identifying the mechanisms of acquired drug resistance has become a hotspot in current researches. Many researches have suggested that tumor microenvironment plays an important role in mediating acquired drug resistance and confers resistance to physiologic mediators of cell death. The specific niches within it may provide a sanctuary for subpopulations of tumor cells that affords a survival advantage following initial drug exposure and may promote acquired drug resistance. Our review focused on tumor microenvironment and its role in mediating acquired drug resistance.