Research progress in drug repurposing in the treatment of breast cancer

doi:10.3969/j.issn.1674-8115.2024.11.013

Abstract

Abstract:

Breast cancer has become one of the most prevalent cancers among women worldwide, posing a significant burden on their health. Current standard therapies are often expensive and associated with the risk of drug resistance. Drug repurposing has gained increasing attention as a cost-effective and time-saving strategy in pharmaceutical research. Many drugs already in clinical use or undergoing clinical trials can be repurposed for the treatment of new clinical indications. Based on a comprehensive understanding of the mechanisms of action of these drugs and the pathophysiological processes of breast cancer, researchers can better identify drugs with potential anti-breast cancer properties and translate them into clinical practice. This paper provides a review of the current research on repurposing existing drugs for breast cancer treatment, summarizes the mechanisms of action of these drugs, and discusses the challenges associated with the strategy of drug repurposing.

Key words: drug repurposing, breast cancer, chemotherapy, anti-tumor

CLC Number:

R730.5

TAN Chen, XU Zhangrun, XUE Yang, CHEN Jiayu, YAO Lijun. Research progress in drug repurposing in the treatment of breast cancer[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(11): 1454-1459.

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References 49

1	BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263.
2	FISUSI F A, AKALA E O. Drug combinations in breast cancer therapy[J]. Pharm Nanotechnol, 2019, 7(1): 3-23.
3	SCHIPPER L J, ZEVERIJN L J, GARNETT M J, et al. Can drug repurposing accelerate precision oncology?[J]. Cancer Discov, 2022, 12(7): 1634-1641.
4	XIA Y, SUN M, HUANG H, et al. Drug repurposing for cancer therapy[J]. Signal Transduct Target Ther, 2024, 9: 92.
5	REN J, WANG B, WU Q, et al. Combination of niclosamide and current therapies to overcome resistance for cancer: new frontiers for an old drug[J]. Biomed Pharmacother, 2022, 155: 113789.
6	GYAMFI J, LEE Y H, MIN B S, et al. Niclosamide reverses adipocyte induced epithelial-mesenchymal transition in breast cancer cells via suppression of the interleukin-6/STAT3 signalling axis[J]. Sci Rep, 2019, 9: 11336.
7	KIM J H, PARK S, JUNG E, et al. A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis[J]. Proc Natl Acad Sci USA, 2023, 120(21): e2304081120.
8	SANSONE P, STORCI G, TAVOLARI S, et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland[J]. J Clin Invest, 2007, 117(12): 3988-4002.
9	ASGEIRSSON K S, OLAFSDÓTTIR K, JÓNASSON J G, et al. The effects of IL-6 on cell adhesion and e-cadherin expression in breast cancer[J]. Cytokine, 1998, 10(9): 720-728.
10	KORKAYA H, KIM G I, DAVIS A, et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2⁺ breast cancer by expanding the cancer stem cell population[J]. Mol Cell, 2012, 47(4): 570-584.
11	LIU H, YAN R, XIAO Z, et al. Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling[J]. Breast Cancer Res, 2023, 25(1): 43.
12	TERRY M B, GAMMON M D, ZHANG F F, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk[J]. JAMA, 2004, 291(20): 2433-2440.
13	LØFLING L, STØER N C, NAFISI S, et al. Low-dose aspirin and risk of breast cancer: a Norwegian population-based cohort study of one million women[J]. Eur J Epidemiol, 2023, 38(4): 413-426.
14	LI W, ZHANG Z, WANG B, et al. MicroRNA and cyclooxygenase-2 in breast cancer[J]. Clin Chim Acta, 2021, 522: 36-44.
15	LI J, HAO Q, CAO W, et al. Celecoxib in breast cancer prevention and therapy[J]. Cancer Manag Res, 2018, 10: 4653-4667.
16	BOWERS L W, MAXIMO I X, BRENNER A J, et al. NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions[J]. Cancer Res, 2014, 74(16): 4446-4457.
17	HAMY A S, TURY S, WANG X, et al. Celecoxib with neoadjuvant chemotherapy for breast cancer might worsen outcomes differentially by COX-2 expression and ER status: exploratory analysis of the REMAGUS02 trial[J]. J Clin Oncol, 2019, 37(8): 624-635.
18	MATTHEWS H K, BERTOLI C, DE BRUIN R A M. Cell cycle control in cancer[J]. Nat Rev Mol Cell Biol, 2022, 23: 74-88.
19	HIGHLEY M S, LANDUYT B, PRENEN H, et al. The nitrogen mustards[J]. Pharmacol Rev, 2022, 74(3): 552-599.
20	WAKS A G, WINER E P. Breast cancer treatment: a review[J]. JAMA, 2019, 321(3): 288-300.
21	SHI K, WANG G, PEI J, et al. Emerging strategies to overcome resistance to third-generation EGFR inhibitors[J]. J Hematol Oncol, 2022, 15(1): 94.
22	LI C L, FANG Z X, WU Z, et al. Repurposed itraconazole for use in the treatment of malignancies as a promising therapeutic strategy[J]. Biomed Pharmacother, 2022, 154: 113616.
23	JIN M, ZENG B, LIU Y, et al. Co-delivery of repurposing itraconazole and VEGF siRNA by composite nanoparticulate system for collaborative anti-angiogenesis and anti-tumor efficacy against breast cancer[J]. Pharmaceutics, 2022, 14(7): 1369.
24	KHAN S, SHUKLA S, FARHAN M, et al. Centchroman prevents metastatic colonization of breast cancer cells and disrupts angiogenesis via inhibition of RAC1/PAK1/β-catenin signaling axis[J]. Life Sci, 2020, 256: 117976.
25	GÖBEL A, RAUNER M, HOFBAUER L C, et al. Cholesterol and beyond: the role of the mevalonate pathway in cancer biology[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873(2): 188351.
26	JIANG W, HU J W, HE X R, et al. Statins: a repurposed drug to fight cancer[J]. J Exp Clin Cancer Res, 2021, 40(1): 241.
27	BAI F, YU Z, GAO X, et al. Simvastatin induces breast cancer cell death through oxidative stress up-regulating miR-140-5p[J]. Aging (Albany NY), 2019, 11(10): 3198-3219.
28	YULIAN E D, SIREGAR N C, BAJUADJI. Combination of simvastatin and FAC improves response to neoadjuvant chemotherapy in locally advanced breast cancer[J]. Cancer Res Treat, 2021, 53(4): 1072-1083.
29	FELDT M, BJARNADOTTIR O, KIMBUNG S, et al. Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial[J]. J Transl Med, 2015, 13: 133.
30	YU M, LI R, ZHANG J. Repositioning of antibiotic levofloxacin as a mitochondrial biogenesis inhibitor to target breast cancer[J]. Biochem Biophys Res Commun, 2016, 471(4): 639-645.
31	NIKAS I P, PASCHOU S A, RYU H S. The role of nicotinamide in cancer chemoprevention and therapy[J]. Biomolecules, 2020, 10(3): E477.
32	JUNG M, LEE K M, IM Y, et al. Nicotinamide (niacin) supplement increases lipid metabolism and ROS-induced energy disruption in triple-negative breast cancer: potential for drug repositioning as an anti-tumor agent[J]. Mol Oncol, 2022, 16(9): 1795-1815.
33	EVANS J M, DONNELLY L A, EMSLIE-SMITH A M, et al. Metformin and reduced risk of cancer in diabetic patients[J]. BMJ, 2005, 330(7503): 1304-1305.
34	HUA Y, ZHENG Y, YAO Y, et al. Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing[J]. J Transl Med, 2023, 21(1): 403.
35	AMARAL I, SILVA C, CORREIA-BRANCO A, et al. Effect of metformin on estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells[J]. Biomed Pharmacother, 2018, 102: 94-101.
36	MAHMOUDI G, EHTESHAMINIA Y, KOKHAEI P, et al. Enhancement of targeted therapy in combination with metformin on human breast cancer cell lines[J]. Cell Commun Signal, 2024, 22(1): 10.
37	ZANNELLA V E, DAL PRA A, MUADDI H, et al. Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response[J]. Clin Cancer Res, 2013, 19(24): 6741-6750.
38	MADAK J T, BANKHEAD A, CUTHBERTSON C R, et al. Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer[J]. Pharmacol Ther, 2019, 195: 111-131.
39	BROWN K K, SPINELLI J B, ASARA J M, et al. Adaptive reprogramming of De novo pyrimidine synthesis is a metabolic vulnerability in triple-negative breast cancer[J]. Cancer Discov, 2017, 7(4): 391-399.
40	LU C, LI X Y, REN Y Y, et al. Disulfiram: a novel repurposed drug for cancer therapy[J]. Cancer Chemother Pharmacol, 2021, 87(2): 159-172.
41	SKROTT Z, MISTRIK M, ANDERSEN K K, et al. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4[J]. Nature, 2017, 552: 194-199.
42	LIU C, QIANG J, DENG Q, et al. ALDH1A1 activity in tumor-initiating cells remodels myeloid-derived suppressor cells to promote breast cancer progression[J]. Cancer Res, 2021, 81(23): 5919-5934.
43	HOPKINS J L, LAN L, ZOU L. DNA repair defects in cancer and therapeutic opportunities[J]. Genes Dev, 2022, 36(5/6): 278-293.
44	KIM D, NAM H J. PARP inhibitors: clinical limitations and recent attempts to overcome them[J]. Int J Mol Sci, 2022, 23(15): 8412.
45	ZHU H, WEI M, XU J, et al. PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications[J]. Mol Cancer, 2020, 19(1): 49.
46	ROBSON M, IM S A, SENKUS E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation[J]. N Engl J Med, 2017, 377(6): 523-533.
47	LITTON J K, RUGO H S, ETTL J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation[J]. N Engl J Med, 2018, 379(8): 753-763.
48	XIA C, DONG X, LI H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl), 2022, 135(5): 584-590.
49	MORELLO L. More cuts loom for US science[J]. Nature, 2013, 501: 147-148.

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