Bahls Bárbara, Aljnadi Israa M, Emídio Rita, Mendes Eduarda, Paulo Alexandra
Faculty of Pharmacy, Research Institute for Medicines (iMed.Ulisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Biomedicines. 2023 Mar 21;11(3):969. doi: 10.3390/biomedicines11030969.
Cancer is a societal burden demanding innovative approaches. A major problem with the conventional chemotherapeutic agents is their strong toxicity and other side effects due to their poor selectivity. Uncontrolled proliferation of cancer cells is due to mutations, deletions, or amplifications in genes (oncogenes) encoding for proteins that regulate cell growth and division, such as transcription factors, for example, . The direct targeting of the c-MYC protein has been attempted but so far unsuccessfully, as it lacks a definite binding site for the modulators. Meanwhile, another approach has been explored since the discovery that G-quadruplex secondary DNA structures formed in the guanine-rich sequences of the promoter region can downregulate the transcription of this oncogene. Here, we will overview the major achievements made in the last decades towards the discovery of a new class of anticancer drugs targeting G-quadruplexes in the promoter of cancer cells.
癌症是一项需要创新方法应对的社会负担。传统化疗药物的一个主要问题是其选择性差，导致毒性强和其他副作用。癌细胞的不受控制增殖是由于编码调节细胞生长和分裂的蛋白质（如转录因子）的基因（癌基因）发生突变、缺失或扩增。人们曾尝试直接靶向c-MYC蛋白，但迄今为止未获成功，因为它缺乏调节剂的明确结合位点。与此同时，自发现富含鸟嘌呤的启动子区域序列中形成的G-四链体二级DNA结构可下调该癌基因的转录以来，人们探索了另一种方法。在此，我们将概述过去几十年在发现一类靶向癌细胞启动子中G-四链体的新型抗癌药物方面所取得的主要成就。
