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Ref Type Journal Article
PMID (21725213)
Authors Gallant JN, Allen JE, Smith CD, Dicker DT, Wang W, Dolloff NG, Navaraj A, El-Deiry WS
Title Quinacrine synergizes with 5-fluorouracil and other therapies in colorectal cancer.
Journal Cancer biology & therapy
Vol 12
Issue 3
Date 2011 Aug 1
Abstract Text Although treatments have improved patient prognosis in surgically resectable colorectal cancer, new effective drugs with improved safety profiles are needed to improve the currently poor outcomes of patients with recurrent or metastatic colorectal cancer. Quinacrine, a small molecule anti-malarial agent that has activity in giardiasis, lupus, prion disease, and used as a means of non-surgical sterilization, has shown cytotoxic activity across a broad range of cancers. Here, we evaluate the potential of adding quinacrine to anticancer chemotherapeutics and targeted agents as a potential novel combinatorial therapy for advanced colon cancer. We show that quinacrine synergizes with 5-fluorouracil and significantly enhances the cytotoxicity of sorafenib in a panel of 10 human colorectal cancer cell lines, including those with KRAS mutations protein gel blot analysis confirmed that quinacrine's anticancer activity partially arises from its ability to stabilize p53 and lower anti-apoptotic protein levels. In a series of in vivo studies, quinacrine monotherapy lowered the tumor load of nu/nu mice bearing human colorectal cancer xenografts. In combination, quinacrine and 5-Fluorouracil significantly delayed tumor growth of a variety of different xenografts, as compared to each agent administered alone. Our results suggest that the administration of quinacrine in combination with chemotherapeutic agents and targeted agents should be further explored in patients with recurrent, locally advanced, or metastatic colorectal cancer.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown colorectal cancer not applicable Fluorouracil + Quinacrine + Sorafenib Preclinical - Cell culture Actionable In a preclinical study, Acrichine (quinacrine) and Adrucil (5-fluorouracil) synergistically enhanced the cytotoxicity of Nexavar (sorafenib) in human colorectal cancer cell lines in culture (PMID: 21725213). 21725213
Unknown unknown colorectal cancer not applicable Fluorouracil + Quinacrine Preclinical - Cell line xenograft Actionable In a preclinical study, Acrichine (quinacrine) and Adrucil (5-fluorouracil) synergized to inhibit tumor growth in colorectal cancer cell line xenograft models (PMID: 21725213). 21725213