약물 용도 변경으로 암 치료 병목 극복

 

Overcoming cancer therapeutic bottleneck by drug repurposing

https://www.nature.com/articles/s41392-020-00213-8

Overcoming cancer therapeutic bottleneck by drug repurposing - Signal Transduction and Targeted Therapy

요약된 신호 네트워크에 의해 활성화된 약물 용도 변경을 사용하여 암세포의 특징을 표적으로 하는 약물 후보 식별.

 

암 세포의 특징에 기여하는 복잡한 신호 전달 상호 작용은 조정되어 신생물 질환의 복잡성을 합리화할 수 있습니다.

암 기능을 방해하는 약물 후보가 표시됩니다.

Table 1 A total panel of repurposed drugs mentioned in this review

From: Overcoming cancer therapeutic bottleneck by drug repurposing

Cancer hallmarksRepurposed drugOriginal applicationReported targets/pathwaysClinical trials of cancer

Sustaining proliferative signaling	Rapamycin	Immunosuppressant, anti-restenosis agent	mTOR and associated signaling networks	Rectum, breast, prostate cancer etc.
Sustaining proliferative signaling	Prazosin	Hypertension	PKCδ-dependent AKT signaling pathway	Adrenal incidentalomas
Sustaining proliferative signaling	Indomethacin	Rheumatic disease	Shc-ERK axis, PKCζ-p38-DRP1 axis, Wnt/β-catenin	Colorectal, esophageal, ovarian cancer etc.
Evading growth suppressors	Quinacrine	Malaria, giardiasis, rheumatoid arthritis	p53, FACT-CK2-p53 axis	Prostatic, non-small cell lung cancer etc.
Evading growth suppressors	Ritonavir	Human immunodeficiency virus	p53, CDKs-RB axis, AKT-E2F-1-RB axis	Breast cancer, Kaposi’s sarcoma etc.
Resisting cell death	Artemisinin and related-derivatives	Malaria	Ferroptosis, autophagy, oncosis, anoikis	Breast, colorectal, lung cancer etc.
Resisting cell death	Chloroquine and related-derivatives	Malaria, rheumatoid arthritis	Autophagy, PPT1	Pancreatic, breast cancer, chondrosarcoma etc.
Enabling replicative immortality	Curcumin	Dermatological diseases	hTERT, Wnt/β-catenin, Hippo/YAP	Breast, prostate cancer, multiple myeloma etc.
Enabling replicative immortality	Genistein	Menopause, osteoporosis, obesity	hTERT, Wnt/β-catenin	Colorectal, bladder, breast cancer etc.
Inducing angiogenesis	Thalidomide	Sedative, antiemetic	Various proangiogenic factors, VEGF receptor, NF-κB	Prostate, ovarian, colorectal cancer etc.
Inducing angiogenesis	Itraconazole	Antifungal agent	mTOR-cholesterol trafficking, VDAC1, PDGF-Akt–mTOR axis	Prostate, lung cancer etc.
Activating invasion and metastasis	Berberine	Bacterial diarrhea	Ephrin-B2, MMP-2/MMP-9, EMT, miR-101, VEGF	Gastric, colorectal, lung cancer etc.
Activating invasion and metastasis	Niclosamide	Antihelminthic drug	Wnt/β-catenin, STAT3, NF-κB	Colorectal, prostate cancer etc.
Genome instability and mutation	Triamterene	Diuretic	Nucleotide excision repair, thymidylate synthase	Acute myelocytic leukemia etc.
Genome instability and mutation	Mebendazole and related-derivatives	Intestinal helminthiasis	Chk2, Nbs1, PARP-1, DHODH	Medulloblastoma, glioma, astrocytoma etc.
Tumor-promoting inflammation	Aspirin	Pain, fever	COX-1/2, ANXA1-NF–κB axis, CDX2, COMMD1–RelA axis	Gastrointestinal, esophageal cancer etc.
Tumor-promoting inflammation	Thiocolchicoside	Rheumatologic, orthopedic disorders	NF-κB-related pathways, COX-2	None
Reprogramming energy metabolism	Metformin	Obese type 2 diabetes	AMPK, PI3K-mTOR pathways, BACH1	Prostate, breast, colorectal cancer etc.
Reprogramming energy metabolism	Disulfiram	Alcohol-aversion drug	ALDH, NAD+-dependent proteins	Prostate, breast cancer, melanoma etc.
Evading immune destruction	Rotavirus vaccines, Live 17D	Infectious disease	NF-κΒ, Type I interferon pathways, CTLs, Tregs	None

1. This table lists existing non-oncology agents for cancer therapy in this review, including targeting cancer hallmarks, original application, reported targets or pathways and related clinical trials in cancer treatment (https://clinicaltrials.gov/).