Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of monoclonal antibodies as adjuvants to cancer chemotherapy has drawn considerable interest in recent years, due to the success of several novel agents against a broad range of targets. One such target is EpCAM (aka GA733-2, KSA, 17-1A antigen), a human cell surface glycoprotein expressed on some normal and most neoplastic epithelial cells. It is now widely recognized as having an important role in tumor biology, especially in colorectal cancer, and since its original discovery in the early 1980s, the known mechanism by which it functions has steadily evolved. Initial studies of monoclonal antibodies directed against EpCAM demonstrated the presence of anti-idiotype networks involving both B and T cells, antibody-dependent cell cytotoxicity, and complement mediated cell death as mechanisms of tumor growth inhibition. Recently, a novel receptor for EpCAM has been described that is a member of the inhibitory group of immunoglobulin-like receptors and is present on lymphocytes, monocytes, dendritic cells, and NK cells. Neoplastic cells that interact with this receptor, named LAIR-1, may enact an immunologic escape, and thus confer a selective advantage for their growth and spread. This novel mechanism of action may add to our current understanding of how monoclonal antibodies targeted against EpCAM inhibit tumor growth. Passive vaccination with this antibody may induce a tertiary anti-idiotypic network which correlates with clinical outcome, but the mechanism behind this outcome in select patients with minimal residual disease may additionally involve a novel blockade of tumor specific immunosuppression. This review will focus on the initial discoveries of EpCAM's cellular adhesion properties, its role in normal and neoplastic cell function, its distribution and presumed mechanism of action, and clinical studies of EpCAM as a therapeutic target. Clinical trials of edrecolomab, one such monoclonal antibody, in patients with colon cancer will be reviewed and updated. While phase III trials of edrecolomab have not demonstrated improved efficacy as adjuvant therapy for stage III colon cancer, newer agents with improved affinity, less chimerism, and improved delivery may still demonstrate benefit.
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PMID:EpCAM: A new therapeutic target for an old cancer antigen. 1590 97

New adjuvant therapies are needed for the treatment of stage III colon cancer. The essential fatty acids, linoleic and arachidonic acid enhance tumorigenesis through the cyclooxygenase and lipoxygenase pathways. Leukotriene B4 (LTB4) is a product of 5-lipoxygenase (5-LOX) which has tumor-promoting effects. The LTB4 receptor antagonist, LY293111 inhibited tumor growth and induced apoptosis in vitro. The effectiveness of LY293111, alone and in combination with gemcitabine was investigated in a heterotopic xenograft model in athymic mice using HT29 and LoVo human colonic cancer cells. The combined therapy markedly inhibited tumor growth and could warrant consideration as a new therapeutic option.
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PMID:Effect of LY293111 in combination with gemcitabine in colonic cancer. 1517 19

Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target.
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PMID:Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival. 2643 21