Molecular targets in cancer therapy

Gale, Danielle

doi:10.1016/s0749-2081(03)00047-0

Cited by 10 publications

(4 citation statements)

References 19 publications

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“…Moreover, conventional cytotoxic therapy is often associated with significant morbidity. Recently, molecular targeting therapy has been developed ( 22 ) and monoclonal antibodies against CD20 and HER2/neu have been used for molecular targeting therapy. ( 1–3 ) Also, in recent therapies for malignancies, monoclonal antibodies have emerged as important therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Blockade of bulky lymphoma‐associated CD55 expression by RNA interference overcomes resistance to complement‐dependent cytotoxicity with rituximab

et al. 2005

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Recently, anti-CD20 (rituximab) and anti-Her2/neu (trastuzumab) antibodies have been developed and applied to the treatment of malignant lymphoma and breast cancer, respectively. However, bulky lymphoma is known to be resistant to rituximab therapy, and this needs to be overcome. Fresh lymphoma cells were collected from 30 patients with non-Hodgkin's lymphoma, the expression of CD20 and CD55 was examined by flow cytometry, and complement-dependent cytotoxicity (CDC) assays were carried out. Susceptibility to CDC with rituximab was decreased in a tumor size-dependent manner (r = -0.895, P < 0.0001), but not in a CD20-dependent manner (r = -0.076, P = 0.6807) using clinical samples. One complement-inhibitory protein, CD55, contributed to bulky lymphoma-related resistance to CDC with rituximab. A decrease in susceptibility to CDC with rituximab was statistically dependent on CD55 expression (r = -0.927, P < 0.0001) and the relationship between tumor size and CD55 expression showed a significant positive correlation (r = 0.921, P < 0.0001) using clinical samples. To overcome the resistance to rituximab by high expression of CD55 in bulky lymphoma masses, small interfering RNA (siRNA) was designed from the DNA sequence corresponding to nucleic acids 1-380 of the CD55 cDNA.

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Section: Discussionmentioning

confidence: 99%

Blockade of bulky lymphoma‐associated CD55 expression by RNA interference overcomes resistance to complement‐dependent cytotoxicity with rituximab

et al. 2005

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“…The super family is also of interest as it is involved in a variety of effects on cell function, and is intimately involved in cross-talk with convergent and divergent pathways involved in cell survival [2][3][4][5][6][7]. A number of studies have demonstrated these potential targets to be overexpressed in numerous tumors, thus leading to the development of both monoclonal antibodies and small molecules to inhibit its function [9,10] with the hope that the target plays a vital role in human malignancy. A number of studies have demonstrated these potential targets to be overexpressed in numerous tumors, thus leading to the development of both monoclonal antibodies and small molecules to inhibit its function [9,10] with the hope that the target plays a vital role in human malignancy.…”

Section: Introductionmentioning

confidence: 99%

Identification of potentially useful combinations of epidermal growth factor receptor tyrosine kinase antagonists with conventional cytotoxic agents using median effect analysis

Budman¹,

Soong²,

Calabro³

et al. 2006

Anti-Cancer Drugs

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Targeted therapy for breast carcinoma has achieved a major advance with the use of trastuzumab in Her2/neu-positive tumors. The epidermal growth factor receptor superfamily thus becomes an attractive target for therapeutic agents. As the epidermal growth factor receptor tyrosine kinase family has a conformational binding site, which allows small molecules to interfere with its function, we have explored the effects of a dual kinase (epidermal growth factor receptor-1 and epidermal growth factor receptor-2) inhibitor (GW282974X) with a variety of cytotoxic agents looking for synergistic effects in vitro. Using a median effect model in four breast cancer cell lines in vitro, cytotoxic agents commonly used in treatment of human malignant disease were combined with trastuzumab or one of two epidermal growth factor receptor tyrosine kinase inhibitors in a 72-h culture and then analyzed for cytotoxic effect by 3-[26]-2,5-diphenyl-tetrazolium bromide assay. Combination index values within one standard deviation of unity were considered additive, less than unity as synergistic and more than unity as antagonistic. Synergistic results were confirmed by curve shift analysis and by an enzyme-linked immunosorbent assay measuring apoptosis by cytoplasmic histone-associated DNA fragments. Quantitative real-time polymerase chain reaction analysis was used to measure the expression of three of the critical enzymes in 5'-deoxy-5-fluorouridine metabolism and activity: thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidine synthase. 5'-Deoxy-5-fluorouridine with GW282974X demonstrated global synergy, both in high and low expressing epidermal growth factor receptor breast cancer cell lines. These results were confirmed by apoptosis assay and cell counts. RNA quantification following treatment with the dual kinase inhibitor suggested reduction in thymidine synthase levels to be a potential mechanism of synergy. The triplet of trastuzumab, GW282974X and 5'-deoxy-5-fluorouridine, and the triplet of GW282974X, epirubicin and 5'-deoxy-5-fluorouridine were highly synergistic in low expression cells (MCF7/wt) and high expression cells (MCF7/adr). These experiments suggest further studies of the dual kinase inhibitor with selected cytotoxics such as 5'-deoxy-5-fluorouridine are warranted.

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“…Drugs that target integrin α v β 3 /α v β 5 and its ligands, including cilengitide, vitaxin, and CNTO 95 [32], have been evaluated in recent clinical trials. However, phase III trials show that Cilengitide, which specifically binds to integrin α v β 3 /α v β 5 receptors, in combination with temozolomide failed to improve survival in GBM patients [33, 34].…”

Section: Discussionmentioning

confidence: 99%

Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway

et al. 2017

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Recent studies have shown that increased syndecan-1 (SDC1) expression in human glioma is associated with higher tumor grades and poor prognoses, but its oncogenic functions and the underlying molecular mechanisms remain unknown. Here, we examined SDC1 expression in datasets from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus. Elevated SDC1 expression in glioma was closely associated with increases in tumor progression and shorter survival. We also examined SDC1 expression and evaluated the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown attenuated proliferation and invasion by glioma cells and markedly decreased PCNA and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased phosphorylation of the c-Src/FAK complex and its downstream signaling molecules, Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic target in the treatment of glioma.

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Molecular targets in cancer therapy

Cited by 10 publications

References 19 publications

Blockade of bulky lymphoma‐associated CD55 expression by RNA interference overcomes resistance to complement‐dependent cytotoxicity with rituximab

Blockade of bulky lymphoma‐associated CD55 expression by RNA interference overcomes resistance to complement‐dependent cytotoxicity with rituximab

Identification of potentially useful combinations of epidermal growth factor receptor tyrosine kinase antagonists with conventional cytotoxic agents using median effect analysis

Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway

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