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|Ref Type||Journal Article|
|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|
|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.|
|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||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|
|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|