A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network
Table 6
Literature evidences for the promising drug candidates for breast cancer.
Promising drugs
Biological validation
Related literature for possible usage for breast cancer
MS-275
o
(i) [45]: the potential anticancer activity of MS-275 in combination with pentoxifylline in panel of cell lines and human breast cancer xenograft model in vitro and in vivo. (ii) [46]: MS-275 sensitizes TRAIL-resistant breast cancer cells, inhibits angiogenesis and metastasis, and reverses epithelial-mesenchymal transition in vivo. (iii) [47]: HDAC inhibitors (MS-275) enhance the apoptosis-inducing potential of TRAIL in breast carcinoma.
GW-8510
⋄
(i) [48]: repositioning of a cyclin-dependent kinase inhibitor GW-8510 as a ribonucleotide reductase M2 inhibitor to treat human colorectal cancer. In addition, GW-8510 induced autophagic cell death. (ii) [49]: in cell viability tests, four candidate drugs, GW-8510, etacrynic acid, ginkgolide A, and 6-azathymine, are identified as having high inhibitory activities against cancer cells.
Camptothecin
o
(i) [50]: the camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer. (ii) [51]: CRLX101, an investigational camptothecin-containing nanoparticle-drug conjugate, targets cancer stem cells and impedes resistance to antiangiogenic therapy in mouse models of breast cancer. (iii) [52]: STI571 sensitizes breast cancer cells to 5-fluorouracil, cisplatin, and camptothecin in a cell type-specific manner. (iv) [53]: acquired camptothecin resistance of human breast cancer MCF-7/C4 cells with normal topoisomerase I and elevated DNA repair. (v) known as “Happy Tree” in Chinese traditional cancer treatment.
Phenoxybenzamine
x
(i) Not enough evidence.
Tyrphostin_AG-825
o
(i) [54]: C-Src activation by ErbB2 leads to attachment-independent growth of human breast epithelial cells. (ii) [55]: using in vivo mouse models of breast cancer: using gefitinib, ERBB1 inhibition rapidly inhibits tumor cell motility and invasion but not intravasation, whereas ERBB2 inhibition by AG825 rapidly blocks intravasation. (iii) [56]: tyrphostin AG 825 has been used in combination with hypericin-mediated photodynamic therapy (HY-PDT) for evaluating its therapeutic effects in HER2 overexpressing human breast cancer cells.
Alsterpaullone
o
(i) [57]: the antitumor effects of ALP through induction of apoptosis in breast cancer and leukemia cells. Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma. (ii) [58]: baicalein blocked survivin expression in lung and breast cancer cells. Alsterpaullone is a CDC2 kinase inhibitor (43). Both CDC25 phosphatase and CDC2 kinase inhibitors enhanced the baicalein-induced cancer cell death.
Celastrol
o
(i) [59]: anticancer effect of celastrol on human triple negative breast cancer: possible involvement of oxidative stress, mitochondrial dysfunction, apoptosis, and PI3K/Akt pathways. (ii) [60]: celastrol induces that apoptosis of breast cancer cells and inhibits invasion via downregulation of MMP-9.
