Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metastatic. In this context, drug repurposing has emerged as a promising strategy to improve treatment options due to the limited number of effective treatments and the heterogeneity of the disease. Indeed, a large number of non-oncology drugs have the potential to address more than one target that could be therapeutic for cancer patients. Although many repurposed drugs are used off-label, efficacy for the new use must be demonstrated in clinical trials. Within regulatory frameworks, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have procedures to reduce the need for extensive new studies and to expedite the review of drugs for serious conditions when preliminary evidence indicates substantial clinical improvement over available therapy. In spite of several advantages, including reduced development time, lower costs, known safety profiles, and faster regulatory approval, difficulty in obtaining new patents for old drugs with limited protection for intellectual property may reduce commercial returns and disincentivize investments. This review aims to provide comprehensive information on some marketed drugs currently under investigation to be repurposed or used in clinical practice for NETs and to discuss the major clinical challenges. Although drug repurposing is a useful strategy for early access to medicines, the monitoring of the clinical benefit of oncologic drugs during the post-marketing authorization is crucial to support the safety and effectiveness of treatments.
药物再利用或药物重定位是指为已批准或研究中的药物寻找超出原始治疗适应症的新治疗用途的过程。在癌症治疗领域，新药发现需要这种成本效益高、节省时间的替代策略，以替代传统药物开发，从而在II/III期研究中实现快速临床转化，尤其针对未满足的医疗需求和罕见疾病。神经内分泌肿瘤（NETs）是一组源于神经内分泌系统细胞的罕见异质性肿瘤，虽然通常呈惰性，但也可能具有侵袭性和转移性。在此背景下，由于有效治疗方法有限且疾病异质性高，药物再利用已成为改善治疗选择的一种有前景的策略。事实上，大量非肿瘤药物具有针对多个靶点的潜力，可能对癌症患者产生治疗效果。尽管许多再利用药物属于超说明书使用，但新用途的疗效仍需通过临床试验验证。在监管框架内，美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）均设有相关程序，以减少广泛新研究的需求，并在初步证据表明药物对严重疾病具有优于现有疗法的临床改善时加速审评。尽管药物再利用具有诸多优势，包括缩短开发时间、降低成本、已知安全性数据以及更快的监管批准，但旧药难以获得新专利且知识产权保护有限，可能降低商业回报并抑制投资积极性。本综述旨在全面介绍目前正在研究或临床实践中用于NETs的某些已上市药物的再利用情况，并讨论主要的临床挑战。尽管药物再利用是早期获取药物的有效策略，但在上市后授权期间对肿瘤药物临床获益的监测对于支持治疗的安全性和有效性至关重要。
Drug Repurposing of New Treatments for Neuroendocrine Tumors
肿瘤(癌症)患者之家