Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh 201303, India; Drug Discovery, Jubilant Biosys, Greater Noida, Noida, Uttar Pradesh, India.
Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh 201303, India.
Semin Cancer Biol. 2024 May;100:17-27. doi: 10.1016/j.semcancer.2024.03.001. Epub 2024 Mar 15.
Cancer cells reprogram their metabolism to become "glycolysis-dominant," which enables them to meet their energy and macromolecule needs and enhancing their rate of survival. This glycolytic-dominancy is known as the "Warburg effect", a significant factor in the growth and invasion of malignant tumors. Many studies confirmed that members of the GLUT family, specifically HK-II from the HK family play a pivotal role in the Warburg effect, and are closely associated with glucose transportation followed by glucose metabolism in cancer cells. Overexpression of GLUTs and HK-II correlates with aggressive tumor behaviour and tumor microenvironment making them attractive therapeutic targets. Several studies have proven that the regulation of GLUTs and HK-II expression improves the treatment outcome for various tumors. Therefore, small molecule inhibitors targeting GLUT and HK-II show promise in sensitizing cancer cells to treatment, either alone or in combination with existing therapies including chemotherapy, radiotherapy, immunotherapy, and photodynamic therapy. Despite existing therapies, viable methods to target the glycolysis of cancer cells are currently lacking to increase the effectiveness of cancer treatment. This review explores the current understanding of GLUT and HK-II in cancer metabolism, recent inhibitor developments, and strategies for future drug development, offering insights into improving cancer treatment efficacy.
癌细胞重新编程其代谢以成为“糖酵解主导”，这使它们能够满足其能量和大分子需求，并提高其存活率。这种糖酵解主导被称为“Warburg 效应”，是恶性肿瘤生长和侵袭的重要因素。许多研究证实，GLUT 家族成员，特别是 HK 家族中的 HK-II，在 Warburg 效应中发挥关键作用，并且与癌细胞中的葡萄糖转运和随后的葡萄糖代谢密切相关。GLUTs 和 HK-II 的过度表达与侵袭性肿瘤行为和肿瘤微环境相关，使其成为有吸引力的治疗靶点。几项研究已经证明，调节 GLUTs 和 HK-II 的表达可以改善各种肿瘤的治疗效果。因此，针对 GLUT 和 HK-II 的小分子抑制剂具有单独或与现有治疗方法（包括化疗、放疗、免疫疗法和光动力疗法）联合使用以增强癌细胞对治疗的敏感性的潜力。尽管存在现有疗法，但目前缺乏针对癌细胞糖酵解的可行方法，以提高癌症治疗的效果。本综述探讨了 GLUT 和 HK-II 在癌症代谢中的当前理解、最近的抑制剂开发以及未来药物开发的策略，为提高癌症治疗效果提供了思路。
