Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives.
Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives.
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DOI：
10.3390/cancers12123622
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发表时间：
2020-12-03
期刊：
影响因子：
5.2
通讯作者：
Smolkova B
中科院分区：
文献类型：
--
作者：
Buocikova V;Rios-Mondragon I;Pilalis E;Chatziioannou A;Miklikova S;Mego M;Pajuste K;Rucins M;Yamani NE;Longhin EM;Sobolev A;Freixanet M;Puntes V;Plotniece A;Dusinska M;Cimpan MR;Gabelova A;Smolkova B
尽管癌症治疗取得了进展，但难以治疗的肿瘤亚型仍然是一个挑战。新的多学科方法可以帮助克服目前由肿瘤异质性、癌症干细胞的激活和富集以及获得性耐药性发展所造成的障碍。由于表观遗传药物的不稳定性、毒性和脱靶效应，表观基因组调节目前在实体瘤中不成功，可能通过实施旨在改善乳腺癌患者结局的基于纳米的递送策略来实现。表观遗传失调已被认为是一个关键因素，有助于对标准化疗的耐药性的发展和乳腺癌的进展，通过上皮间质转化。尽管第一代表观遗传药物（epi-drugs）在实体瘤治疗中的疗效令人失望，但越来越多的证据表明，表观基因组调控与其他治疗方法协同作用，可以在癌症治疗中发挥重要作用，逆转获得性治疗耐药性。然而，实体恶性肿瘤的表观遗传治疗并不简单。应用于医学的纳米技术的出现为推进表观药物的靶向递送带来了新的机会，同时提高了其稳定性和溶解性，并最大限度地减少了脱靶效应。此外，组学技术，作为强大的分子流行病学筛查工具，使新的诊断和预后表观遗传生物标志物鉴定，允许患者分层和定制管理。与新一代表观药物相结合，纳米医学可以帮助克服耐药肿瘤的低疗效。本文综述了目前正在进行的临床试验，重点是采用表观药物治疗乳腺癌的联合治疗，并总结了最新的纳米靶向给药的表观药物的方法。此外，它强调了目前的局限性和障碍与应用这些实验策略在诊所。
Despite advances in cancer treatment, difficult-to-treat tumor subtypes remain a challenge. New multidisciplinary approaches can help overcome current obstacles posed by tumor heterogeneity, activation and enrichment of cancer stem cells, and acquired drug resistance development. Epigenome modulation, currently unsuccessful in solid tumors due to epigenetic drug instability, toxicity, and off-target effects, might be enabled by implementing nano-based delivery strategies aiming to improve breast cancer patient outcomes. Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identification, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics.
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