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Ref Type Journal Article
PMID (24100628)
Authors Liu T, Hu W, Dalton HJ, Choi HJ, Huang J, Kang Y, Pradeep S, Miyake T, Song JH, Wen Y, Lu C, Pecot CV, Bottsford-Miller J, Zand B, Jennings NB, Ivan C, Gallick GE, Baggerly KA, Hangauer DG, Coleman RL, Frumovitz M, Sood AK
Title Targeting SRC and tubulin in mucinous ovarian carcinoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 19
Issue 23
Date 2013 Dec 01
URL
Abstract Text To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma.The in vitro and in vivo effects and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin polymerization, were examined in mucinous ovarian cancer models.In vitro studies using RMUG-S and RMUG-L cell lines showed that KX-01 inhibited cell proliferation, induced apoptosis, arrested the cell cycle at the G2-M phase, and enhanced the cytotoxicity of oxaliplatin in the KX-01-sensitive cell line, RMUG-S. In vivo studies showed that KX-01 significantly decreased tumor burden in RMUG-S and RMUG-L mouse models relative to untreated controls, and the effects were greater when KX-01 was combined with oxaliplatin. KX-01 alone and in combination with oxaliplatin significantly inhibited tumor growth by reducing cell proliferation and inducing apoptosis in vivo. PTEN knock-in experiments in RMUG-L cells showed improved response to KX-01. Reverse phase protein array analysis showed that in addition to blocking downstream molecules of Src family kinases, KX-01 also activated acute stress-inducing molecules.Our results showed that targeting both the Src pathway and tubulin with KX-01 significantly inhibited tumor growth in preclinical mucinous ovarian cancer models, suggesting that this may be a promising therapeutic approach for patients with mucinous ovarian carcinoma.

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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
PTEN wild-type ovarian mucinous neoplasm sensitive KX2-391 Preclinical Actionable In a preclinical study, KX2-391 inhibited survival of PTEN wild-type mucinous ovarian carcinoma cell lines in culture, and reduced tumor growth in xenograft models (PMID: 24100628). 24100628
PTEN loss ovarian mucinous neoplasm no benefit KX2-391 + Oxaliplatin Preclinical Actionable In a preclinical study, KX2-391 and Eloxatin (oxaliplatin) combination treatment did not show improved tumor suppression in xenograft models of ovarian mucinous carcinoma harboring PTEN loss when compared to single agent treatment (PMID: 24100628). 24100628
PTEN wild-type ovarian mucinous neoplasm sensitive KX2-391 + Oxaliplatin Preclinical Actionable In a preclinical study, KX2-391 and Eloxatin (oxaliplatin) synergistically inhibited survival of PTEN wild-type mucinous ovarian carcinoma cell lines in culture, and reduced tumor growth in xenograft models (PMID: 24100628). 24100628
PTEN loss ovarian mucinous neoplasm decreased response KX2-391 Preclinical Actionable In a preclincal study, mucinous ovarian carcinoma cell lines harboring PTEN loss were less sensitive to KX2-391 induced growth inhibition in culture and tumor suppression in xenograft models (PMID: 24100628). 24100628
PTEN G129R ovarian mucinous neoplasm decreased response KX2-391 Preclinical Actionable In a preclincal study, mucinous ovarian carcinoma cell lines over-expressing PTEN G129R were less sensitive to KX2-391 induced growth inhibition in culture and tumor suppression in xenograft models (PMID: 24100628). 24100628