Sarkar Pritam, Sultana Nasrin, Debnath Prottoy Kumar, Rouf Razina, Mubarak Mohammad S, Uddin Shaikh Jamal, Popa Dragoş, Calina Daniela, Sharifi-Rad Javad
Pharmacy Discipline, Khulna University, Khulna, Bangladesh.
Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj, Bangladesh.
Arch Pharm (Weinheim). 2025 Sep;358(9):e70084. doi: 10.1002/ardp.70084.
Despite notable advancements in conventional cancer therapies, challenges such as drug resistance, adverse effects, and high treatment costs remain significant obstacles. This situation calls for exploring new therapeutic options. One promising approach is drug repurposing, which uses existing medications with known effects to identify new anticancer agents. Isotretinoin (13-cis-retinoic acid), a vitamin A derivative typically used to treat severe acne, shows considerable potential as an anticancer agent. Recent studies suggest that isotretinoin has the potential to enhance the efficacy of cancer treatment and contribute to cancer inhibition by targeting specific molecular pathways. This review explores isotretinoin's chemistry, pharmacokinetics, and toxicity, emphasizing its role in cancer treatment through clinical and preclinical studies while elucidating its anticancer mechanisms. Both preclinical and clinical studies have revealed that isotretinoin can effectively inhibit the growth of tumor cells, induce apoptosis, and help regulate cellular differentiation in a range of cancers, including neuroblastoma, glioblastoma, breast, skin, lung, ovarian, cervical, and head and neck cancers. Isotretinoin works against cancer through several mechanisms. It activates retinoic acid receptors (RARs), suppresses oncogenic signaling pathways, and influences gene transcription related to cell cycle control and apoptosis. Moreover, combining isotretinoin with other treatments, like interferon-alpha, chemotherapy drugs, or other targeted inhibitors, can create synergistic effects that improve treatment effectiveness and potentially lessen side effects. Although isotretinoin holds great promise, we still need more research to address its limitations, such as its toxicity, risks during pregnancy, and differing responses in various cancer types. Current research focuses on optimizing isotretinoin-based therapies by refining dosage regimens to maximize efficacy and enhancing formulation strategies for improved absorption and reduced side effects. Ultimately, the use of isotretinoin in cancer treatment demonstrates the potential of repurposing established drugs and paves the way for more accessible and cost-effective cancer therapies.
尽管传统癌症疗法取得了显著进展，但耐药性、副作用和高昂的治疗成本等挑战仍然是重大障碍。这种情况促使人们探索新的治疗选择。一种有前景的方法是药物重新利用，即利用具有已知作用的现有药物来识别新的抗癌药物。异维甲酸（13-顺式维甲酸）是一种通常用于治疗重度痤疮的维生素A衍生物，作为抗癌药物显示出相当大的潜力。最近的研究表明，异维甲酸有可能通过靶向特定分子途径提高癌症治疗效果并有助于抑制癌症。本综述探讨了异维甲酸的化学性质、药代动力学和毒性，通过临床和临床前研究强调其在癌症治疗中的作用，同时阐明其抗癌机制。临床前和临床研究均表明，异维甲酸可有效抑制肿瘤细胞生长、诱导凋亡，并有助于调节多种癌症（包括神经母细胞瘤、胶质母细胞瘤、乳腺癌、皮肤癌、肺癌、卵巢癌、宫颈癌以及头颈癌）中的细胞分化。异维甲酸通过多种机制对抗癌症。它激活维甲酸受体（RARs），抑制致癌信号通路，并影响与细胞周期控制和凋亡相关的基因转录。此外，将异维甲酸与其他治疗方法（如α干扰素、化疗药物或其他靶向抑制剂）联合使用，可以产生协同效应，提高治疗效果并可能减轻副作用。尽管异维甲酸前景广阔，但我们仍需要更多研究来解决其局限性，如毒性、孕期风险以及不同癌症类型的不同反应。当前的研究重点是通过优化给药方案以最大化疗效，并改进制剂策略以提高吸收和减少副作用，从而优化基于异维甲酸的治疗方法。最终，异维甲酸在癌症治疗中的应用证明了重新利用现有药物的潜力，并为更易获得且成本效益更高的癌症治疗铺平了道路。
