The new paradigm in the treatment of colorectal cancer: are we hitting the right target?

Baranda, Joaquina; Williamson, Stephen K.

doi:10.1517/13543784.16.3.311

Cited by 8 publications

(4 citation statements)

References 97 publications

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“…Numerous molecular alterations in colon cancer have been identified, providing potential targets for colon cancer therapy (2). However, few molecularly targeted therapies have progressed to clinical trials for the treatment of colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase Cβ Is an Effective Target for Chemoprevention of Colon Cancer

et al. 2009

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Colon cancer develops over a period of 10 to 15 years, providing a window of opportunity for chemoprevention and early intervention. However, few molecular targets for effective colon cancer chemoprevention have been characterized and validated. Protein kinase CBII (PKCBII) plays a requisite role in the initiation of colon carcinogenesis in a preclinical mouse model by promoting proliferation and increased B-catenin accumulation. In this study, we test the hypothesis that PKCBII is an effective target for colon cancer chemoprevention using enzastaurin (LY317615), a PKCB-selective inhibitor, in a mouse model of colon carcinogenesis. We find that enzastaurin potently reduces azoxymethane-induced colon tumor initiation and progression by inhibiting PKCBII-mediated tumor cell proliferation and B-catenin accumulation. Biochemically, enzastaurin reduces expression of the PKCBII-and B-catenin/T-cell factor-regulated genes PKCbII, cyclooxygenase II , and vascular endothelial growth factor, three genes implicated in colon carcinogenesis. Our results show that enzastaurin is an effective chemopreventive agent in a mouse model of sporadic colon cancer that significantly reduces both tumor initiation and progression by inhibiting expression of proproliferative genes. Thus, PKCBII is an important target for colon cancer chemoprevention and the PKCB-selective inhibitor enzastaurin may represent an effective chemopreventive agent in patients at high risk for colon cancer.

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Section: Introductionmentioning

confidence: 99%

Protein Kinase Cβ Is an Effective Target for Chemoprevention of Colon Cancer

et al. 2009

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“…4,6,9,10 Furthermore, the survival of abnormal cells is a characteristic feature of cancer. In colorectal tumors, some signal transduction pathways drive abnormal cell growth.…”

Section: Dovepressmentioning

confidence: 99%

“…11,12 Its signaling is a potential target for cancer therapy. 4,5 In treating colorectal cancer, a monoclonal antibody against EGF receptor (EGFR) such as a cetuximab is active, 4,5,[12][13][14] and small-molecular tyrosine kinase inhibitors of EGFRs have been shown to be effective. 4,12 Additionally, one of the hallmarks of human carcinogenesis is the breakdown of cell apoptotic machinery.…”

Section: Dovepressmentioning

confidence: 99%

“…4,5 In treating colorectal cancer, a monoclonal antibody against EGF receptor (EGFR) such as a cetuximab is active, 4,5,[12][13][14] and small-molecular tyrosine kinase inhibitors of EGFRs have been shown to be effective. 4,12 Additionally, one of the hallmarks of human carcinogenesis is the breakdown of cell apoptotic machinery. 15 Overexpression of anti-apoptotic Bcl-2 family members frequently relates to decreased sensitivity to anticancer drugs and radiotherapy in many types of cancer.…”

Section: Dovepressmentioning

confidence: 99%

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Screening of potential molecular targets for colorectal cancer therapy

Honma¹,

Takemasa

Matoba

et al. 2009

IJGM

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Colorectal cancer is a leading cause of cancer death worldwide. To identify molecular targets for colorectal cancer therapy, we tested small interfering RNAs (siRNAs) against 97 genes whose expression was elevated in human colorectal cancer tissues for the ability to promote apoptosis of human colorectal cancer cells (HT-29 cells). The results indicate that the downregulation of PSMA7 (proteasome subunit, α-type, 7) and RAN (ras-related nuclear protein) most efficiently induced apoptosis of HT-29 cells. PSMA7 and RAN were highly expressed in colorectal cancer cell lines compared with normal colon tissues. Furthermore, PSMA7 and RAN were overexpressed in not only colon tumor tissues but also the other tumor tissues. Moreover, in vivo delivery of PSMA7 siRNA and RAN siRNA markedly induced apoptosis in HT-29 xenograft tumors in mice. Thus, silencing of PSMA7 and RAN induces cancer cells to undergo apoptosis, and PSMA7 and RAN might be promising new molecular targets for drug and RNA interference-based therapeutics against colorectal cancer.

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Polyps and Colon Cancer

Thoeni¹,

Laufer²

2008

Textbook of Gastrointestinal Radiology

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The new paradigm in the treatment of colorectal cancer: are we hitting the right target?

Cited by 8 publications

References 97 publications

Protein Kinase Cβ Is an Effective Target for Chemoprevention of Colon Cancer

Protein Kinase Cβ Is an Effective Target for Chemoprevention of Colon Cancer

Screening of potential molecular targets for colorectal cancer therapy

Polyps and Colon Cancer

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