Zhra Mahmoud, Akhund Shahid Akhtar, Mohammad Khalid S
Department of Anatomy, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Apr 3;18(4):520. doi: 10.3390/ph18040520.
Osteosarcoma is recognized as the most prevalent primary bone malignancy, primarily affecting children and adolescents. It is characterized by its aggressive behavior and high metastatic potential, which often leads to poor patient outcomes. Despite advancements in surgical techniques and chemotherapy regimens, the prognosis for patients with osteosarcoma remains unsatisfactory, with survival rates plateauing over the past few decades. A significant barrier to effective treatment is the development of chemotherapy resistance, which complicates the management of the disease and contributes to high rates of recurrence. This review article aims to provide a comprehensive overview of recent advancements in osteosarcoma therapy, particularly in overcoming chemotherapy resistance. We begin by discussing the current standard treatment modalities, including surgical resection and conventional chemotherapy agents such as methotrexate, doxorubicin, and cisplatin. While these approaches have been foundational in managing osteosarcoma, they are often limited by adverse effects and variability in efficacy among patients. To address these challenges, we explore novel pharmacological strategies that aim to enhance treatment outcomes. This includes targeted therapies focusing on specific molecular alterations in osteosarcoma cells and immunotherapeutic approaches designed to harness the body's immune system against tumors. Additionally, we review innovative drug delivery systems that aim to improve the bioavailability and efficacy of existing treatments while minimizing toxicity. The review also assesses the mechanisms underlying chemotherapy resistance, such as drug efflux mechanisms, altered metabolism, and enhanced DNA repair pathways. By synthesizing current research findings, we aim to highlight the potential of new therapeutic agents and strategies for overcoming these resistance mechanisms. Ultimately, this article seeks to inform future research directions and clinical practices, underscoring the need for continued innovation in treating osteosarcoma to improve patient outcomes and survival rates.
骨肉瘤被认为是最常见的原发性骨恶性肿瘤，主要影响儿童和青少年。其特点是具有侵袭性和高转移潜力，这往往导致患者预后不良。尽管手术技术和化疗方案有所进步，但骨肉瘤患者的预后仍然不尽人意，在过去几十年中生存率一直停滞不前。有效治疗的一个重大障碍是化疗耐药性的出现，这使疾病的管理变得复杂，并导致高复发率。这篇综述文章旨在全面概述骨肉瘤治疗的最新进展，特别是在克服化疗耐药性方面。我们首先讨论当前的标准治疗方式，包括手术切除和传统化疗药物，如甲氨蝶呤、阿霉素和顺铂。虽然这些方法是治疗骨肉瘤的基础，但它们往往受到副作用和患者疗效差异的限制。为应对这些挑战，我们探索旨在提高治疗效果的新型药理学策略。这包括针对骨肉瘤细胞特定分子改变的靶向治疗和旨在利用人体免疫系统对抗肿瘤的免疫治疗方法。此外，我们还综述了创新的药物递送系统，其旨在提高现有治疗方法的生物利用度和疗效，同时将毒性降至最低。该综述还评估了化疗耐药性的潜在机制，如药物外排机制、代谢改变和DNA修复途径增强。通过综合当前的研究结果，我们旨在突出新治疗药物和克服这些耐药机制的策略的潜力。最终，本文旨在为未来的研究方向和临床实践提供参考，强调在治疗骨肉瘤方面持续创新以改善患者预后和生存率的必要性。
