Combinatorial chemoprevention of intestinal neoplasia

Torrance, C; Jackson, Peta E.; Montgomery, Elizabeth A.; Kinzler, Kenneth W.; Vogelstein, Bert; Wissner, Allan; Nunes, Maria; Frost, Philip; Discafani, Carolyn

doi:10.1038/79534

Cited by 459 publications

(264 citation statements)

References 39 publications

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“…Furthermore, trastuzumab does not induce apoptosis in breast cancer cells, but it is able to increase the ZD1839-induced programmed cell death . In addition, a recent report has shown that EGFR-TKIs increase the ability of non-steroidal antiinflammatory drugs to prevent the formation of intestinal polyps in an experimental murine model of human familial adenomatous polyposis (FAP) (Torrance et al, 2000). Taken together, these observations suggest that combination of different target-based agents might prove extremely efficient in inhibiting the growth of human solid malignancies.…”

Section: Discussionmentioning

confidence: 95%

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action?

Normanno

Maiello

Luca

2002

Journal Cellular Physiology

129

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A range of target-based agents for the treatment of solid tumors are in development. The epidermal growth factor receptor (EGFR) has been identified as a relevant target as it is involved in regulating several cellular functions important in the proliferation and survival of cancer cells, is commonly expressed at high levels in a range of tumors, and high expression is often related to poor prognosis. EGFR is a member of the ErbB family of receptors which also includes ErbB-2, ErbB-3, and ErbB-4. These receptors form dimers of the same type (homodimers) or with other family members (heterodimers), each combination resulting in different downstream effects. Some of the most advanced targeted agents in development are the EGFR tyrosine kinase inhibitors (EGFR-TKIs), of which ZD1839 ('Iressa') is an example. In Phase II monotherapy trials, oral ZD1839 was well tolerated and demonstrated clinically meaningful antitumor activity and symptom relief in pretreated patients with advanced NSCLC. Preclinical studies have suggested that the antitumor activity of ZD1839 does not depend on the level of EGFR expression. Furthermore, in addition to an effect on EGFR signaling, treatment with ZD1839 as well as with other quinazoline EGFR-TKIs, may also affect signaling of other ErbB family members. EGFR-TKIs have been shown in preclinical studies to increase the efficacy of cytotoxic drugs and Phase III trials of such combinations are ongoing. On the basis that different signal transduction pathways contribute to the control of tumor growth, future therapeutic approaches are likely to involve combination of different targeted agents.

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Section: Discussionmentioning

confidence: 95%

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action?

Normanno

Maiello

Luca

2002

Journal Cellular Physiology

129

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“…To facilitate examination of the colon, tissue samples were "Swiss rolled" prior to embedding and sectioning. 21 Cecal and colon sections were graded for inflammation using a scale of 0 (no inflammation), +1 (mild increase in inflammatory cells; no mucosal changes), +2 (moderate increase in inflammatory cells; mild scattered proliferation +/− focal loss of crypt architecture), +3 (severe increase in inflammatory cells; diffuse or nearly diffuse proliferation, focally extensive loss of crypt architecture), +4 (complete or nearly complete mucosal destruction).…”

Section: Histologymentioning

confidence: 99%

Enterotoxigenic Bacteroides fragilis: A potential instigator of colitis

Rabizadeh

Rhee

et al. 2007

Inflammatory Bowel Diseases

121

102

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Background-Inflammatory bowel disease (IBD) is proposed to result from a dysregulated mucosal immune response to the colonic flora in genetically susceptible individuals. Enterotoxigenic Bacteroides fragilis (ETBF), a molecular subclass of the common human commensal, B. fragilis, has been associated with IBD. This study investigated whether ETBF colonization of mice initiated colitis or modified the clinical course of a colitis agonist, dextran sodium sulfate (DSS).

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“…The above molecules have been shown to synergise in vitro and in animal models the effects of conventional anticancer agents (Ciardiello et al, 2000). First, treatments based on combination therapy with NSAIDs and compounds that target other oncogenic pathways have been successfully tested in chemopreventive settings: Torrance et al (2000) showed that combination treatment of APCmin mice with sulindac and the ErbB tyrosine kinase inhibitor EKI-569 resulted in synergistic antitumour activity that leads to complete polyp prevention in half of all treated mice. Then, DuBois and collaborators, in the field of cancer therapy, clearly showed that the combination of celecoxib and herceptin had additive effects against the HCA rectal adenocarcinoma cell line in vitro and in xenograft, which leads to the almost complete inhibition of tumour growth (Mann et al, 2001).…”

Section: Further Attractive Combination Therapymentioning

confidence: 99%

Nonsteroidal anti-inflammatory drugs in colorectal cancer: from prevention to therapy

et al. 2003

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In this review, we discuss the available experimental evidences supporting the chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) on colorectal cancer and the biological basis for their possible role as anticancer agents. Although the comprehension of the mechanisms underlying the effects of these drugs on colon cancer cells is incomplete, research efforts in identifying the biochemical pathway by which NSAIDs exert their chemopreventive effect have provided a rationale for the potential use of NSAIDs alone or in combination with conventional and experimental anticancer agents in the treatment of colorectal cancer. In this paper, we review three main issues: (i) the role of COX-2 in colon cancer; (ii) the common death pathways between NSAIDs and anticancer drugs; and (iii) the biological basis for the combination therapy with COX-2 selective inhibitors and new selective inhibitors of growth factor signal transduction pathways. ROLE OF COX-2 IN COLON CANCERColorectal cancer is the third most common cancer in the world, and the second most common cause of cancer-related death. Despite the development of new strategies of aggressive surgical and adjuvant therapy, little progress has been made in the successful management of advanced disease; therefore, much hope is currently placed on chemoprevention.A large body of evidence from epidemiological studies and clinical trials in patients with the hereditary colon cancer syndrome, familial adenomatous polyposis coli (FAP) indicates that aspirin and related drugs, known as nonsteroidal antiinflammatory drugs (NSAIDs), which share the property of inhibiting the cyclooxygenase (COX) enzyme, hinder the development of colon cancer and perhaps other cancers as well.COX is the rate-limiting enzyme for the synthesis of eicosanoids, such as prostaglandins, from arachidonic acid. Two COX isoforms have been identified: the constitutively expressed COX-1 and the inducible COX-2. COX-1 is a housekeeping gene and has an important role in protecting the gastroduodenal mucosa. The COX-2 gene, an immediate-early response gene, is rapidly induced in response to tumour promoters, cytokines, and growth factors Di Popolo et al, 2000). NSAIDs may achieve different degrees of inhibition of COX-1 and COX-2 and can be grouped into selective and nonselective inhibitors of COX-2.The development of COX-2-specific inhibitors, like celecoxib and rofecoxib, drugs that maintain their anti-inflammatory properties while preserving the biosynthesis of protective prostaglandins, further raised interest in this field. A large body of research was therefore performed to clarify the relative involvement of the two COX isoforms in colorectal carcinogenesis and the role of COX-2-selective inhibitors as chemopreventive agents.COX-2, but not COX-1, expression was found to be increased in colorectal cancer (Eberhart et al, 1994): approximately 50% of adenomas and 80 -85% of adenocarcinomas showed increased expression of COX-2. This observation was later confirmed by other investigators. Mo...

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Combinatorial chemoprevention of intestinal neoplasia

Cited by 459 publications

References 39 publications

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action?

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs): Simple drugs with a complex mechanism of action?

Enterotoxigenic Bacteroides fragilis: A potential instigator of colitis

Nonsteroidal anti-inflammatory drugs in colorectal cancer: from prevention to therapy

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