Novel targeted therapies for advanced esophageal cancer

Lin, Chien-Feng; Papadopoulos, K.

doi:10.1111/j.1442-2050.2007.00730.x

Cited by 11 publications

(8 citation statements)

References 79 publications

(168 reference statements)

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“…Esophageal cancer accounts for an estimated 400,000 deaths annually (Smith et al, 2008) and is the sixth leading cause of cancer‐related deaths worldwide (Lin and Papadopoulos, 2007). The two major tumor types, squamous cell carcinoma and adenocarcinoma are highly aggressive malignancies which in most cases, require surgical removal of a large portion of the affected esophagus (Mariette et al, 2007; Wu and Posner, 2003).…”

Section: Introductionmentioning

confidence: 99%

Esophageal tissue engineering: An in‐depth review on scaffold design

Tan

Chua

Leong

et al. 2011

Biotech & Bioengineering

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Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design.

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Section: Introductionmentioning

confidence: 99%

Esophageal tissue engineering: An in‐depth review on scaffold design

Tan

Chua

Leong

et al. 2011

Biotech & Bioengineering

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“…Moreover, while the evidence suggests a strong association between ERBB1 expression and response to targeted therapy in EC, it is less well established in the case of ERBB2 (13)(14)(15)17,18). Here, we found that cetuximab inhibited cellular proliferation in the EC cell lines while trastuzumab had no effect, but the combination of the two had a greater inhibitory effect than cetuximab alone.…”

Section: Discussionmentioning

confidence: 44%

“…A number of review articles have reported on the variability of ERBB-receptor expression levels in EC (13)(14)(15)18,17). Here, we found ERBB1 and ERBB2 overexpression of 84 and 30%, respectively, as determined from IHC staining intensity of 3+ or 2+.…”

Section: Discussionmentioning

confidence: 54%

“…Numerous studies conducted in EC patients and cell lines have reported overexpression of ERBB1 and ERBB2 as well as a correlation between ERBB1 and ERBB2 expression and prognosis, although some contrary findings have also been reported (13)(14)(15)(16)(17)(18)(19)(20). Given the important role ERBB receptor signaling may play in the progression of EC, it has been reasoned that blocking ERBB1 and ERBB2 might prove an effective strategy for cancer treatment (14,16,(18)(19)(20). Using two well-known anti-ERBB receptor monoclonal antibodies, we sought to further investigate their inhibitory effects on EC cell lines and elucidate some potential mechanisms by which this might occur.…”

Section: Introductionmentioning

confidence: 84%

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Concurrent biological targeting therapy of squamous cell carcinoma of the esophagus with cetuximab and trastuzumab

et al. 2012

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Abstract. The ERBB proteins are cell membrane tyrosine kinase receptors. Among these receptors, ERBB1 (EGFR or HER1) and ERBB2 (HER2/Neu) have been reported to be the most important in terms of the development and progression of squamous cell carcinoma of the esophagus (SCC). Thus, targeting of ERBB1 and ERBB2 may become a promising strategy to treat SCC. In the present study, we examined ERBB1 and ERBB2 expression of SCC cell lines (TT, TE2, TE6 and TE10) and tumor samples. In addition, we evaluated the effect of the anti-ERBB1 antibody cetuximab and the anti-ERBB2 antibody trastuzumab for SCC in vitro and in vivo. Biological activities (receptor downregul ation, the phosphorylation of MAPK and AKT) induced by the two agents were also investigated. Immunohistochemistry of SCC samples showed that ERBB1 was detected in 84%, while ERBB2 was detected in 30%. RT-PCR analysis revealed that ERBB1 and ERBB2 mRNA were detectable in all four cell lines. MTT cell proliferation analysis showed that cetuximab, but not trastuzumab, inhibited growth in each of the SCC cell lines in a dose-dependent manner. Further, cetuximab and trastuzumab used together produced stronger inhibition of growth compared to cetuximab alone. Cetuximab downregulated ERBB1, but not ERBB2, at the TE6 cell surface. However, neither ERBB1 nor ERBB2 showed any downregul ation by trastuzumab at the TE6 cell surface. Cetuximab, not but trastuzumab, inhibited the phosphorylation of MAPK and Akt. When administered in combination, the two agents inhibited Akt phosphorylation to a greater degree compared to treatment with cetuximab alone. In the in vivo study, cetuximab, but not trastuzumab, significantly inhibited the TT tumors. Additionally, the combination of cetuximab with trastuzumab induced a synergistic inhibitory antitumor effect in the TT tumors. In conclusion, combination of cetuximab and trastuzumab revealed a synergistic antitumor effect for SCC in vitro and in vivo. The antitumor effect may be induced by the inhibition of the phosphorylation of Akt. These findings suggest that combination therapy including cetuximab and trastuzumab may be a promising strategy to treat SCC.

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“…Lastly, the search for novel indicators predictive of pathological complete response (pCR), a marker closely linked to overall survival in patients with EC, is another 'hot topic' (68)(69)(70)(71)(72). Residual disease identifies aggressive, chemoradiation-resistant cancer, with a high potential for metastasis.…”

Section: Discussionmentioning

confidence: 99%

Preoperative treatment of locally advanced esophageal carcinoma

Orditura

Galizia

Fabozzi

et al. 2013

International Journal of Oncology

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Esophageal cancer (EC) is an aggressive malignancy with increasing incidence worldwide. Surgery is still the most effective treatment, however, both the high rate of local and distant recurrences and surgery-related complications led us to investigate new preoperative strategies. In this review, we discuss the role of neoadjuvant therapy for locally advanced EC with a focus on preoperative chemoradiation (trimodality treatment). Furthermore, the last fifteen years of published literature and our experience have been also reviewed. In the preoperative setting, few trials have reported a significant benefit with fluoropyrimidine and platinum compound-based neoadjuvant chemotherapy, compared to surgery alone. A large number of phase III trials and meta-analyses have demonstrated improved outcomes with preoperative chemoradiation vs. neoadjuvant chemotherapy or surgery alone. Therefore, trimodality therapy can be considered the most effective option in the management of locally advanced EC. Addition of drugs targeting VEGF or HER2 to standard chemotherapy appears to be feasible but needs to be explored more accurately. FDG-PET may predict both response to neoadjuvant treatments and prognosis.

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Novel targeted therapies for advanced esophageal cancer

Cited by 11 publications

References 79 publications

Esophageal tissue engineering: An in‐depth review on scaffold design

Esophageal tissue engineering: An in‐depth review on scaffold design

Concurrent biological targeting therapy of squamous cell carcinoma of the esophagus with cetuximab and trastuzumab

Preoperative treatment of locally advanced esophageal carcinoma

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