Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer

Cancer research of the Warburg effect, a hallmark metabolic alteration in tumors, focused attention on glucose metabolism whose targeting uncovered several agents with promising anticancer effects at the preclinical level. These agents’ monotherapy points to their potential as adjuvant combination therapy to existing standard chemotherapy in human trials. Accordingly, several studies on combining glucose transporter (GLUT) inhibitors with chemotherapeutic agents, such as doxorubicin, paclitaxel, and cytarabine, showed synergistic or additive anticancer effects, reduced chemo-, radio-, and immuno-resistance, and reduced toxicity due to lowering the therapeutic doses required for desired chemotherapeutic effects, as compared with monotherapy. The combinations have been specifically effective in treating cancer glycolytic phenotypes, such as pancreatic and breast cancers. Even combining GLUT inhibitors with other glycolytic inhibitors and energy restriction mimetics seems worthwhile. Though combination clinical trials are in the early phase, initial results are intriguing. The various types of GLUTs, their role in cancer progression, GLUT inhibitors, and their anticancer mechanism of action have been reviewed several times. However, utilizing GLUT inhibitors as combination therapeutics has received little attention. We consider GLUT inhibitors agents that directly affect glucose transporters by binding to them or indirectly alter glucose transport by changing the transporters' expression level. This review mainly focuses on summarizing the effects of various combinations of GLUT inhibitors with other anticancer agents and providing a perspective on the current status. © 2020 Elsevier B.V.

Авторы
Tilekar K.1 , Upadhyay N.1 , Iancu C.V.2 , Pokrovsky V. 3, 4 , Choe J.-Y.2 , Ramaa C.S.1
Издательство
Elsevier B.V.
Номер выпуска
2
Язык
Английский
Статус
Опубликовано
Номер
188457
Том
1874
Год
2020
Организации
  • 1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, Navi Mumbai, Maharashtra, India
  • 2 East Carolina Diabetes and Obesity Institute, Department of Chemistry, East Carolina University, Greenville, NC, United States
  • 3 Laboratory of Combined Therapy, N.N. Blokhin Cancer Research Center, Moscow, Russian Federation
  • 4 Department of Biochemistry, People's Friendship University, Moscow, Russian Federation
Ключевые слова
Cancer; Combination strategy; Drug synergy; Glucose transporters (GLUTs); GLUT inhibitors
Дата создания
20.04.2021
Дата изменения
20.04.2021
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/72554/
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