Targeting the Human Epidermal Growth Factor Receptor 2 in Esophageal Cancer

Almhanna, Khaldoun; Meredith, Kenneth; Hoffe, Sarah E.; Shridhar, Ravi; Coppola, Domenico

doi:10.1177/107327481302000204

Cited by 24 publications

(20 citation statements)

References 26 publications

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“…In this era of molecular oncology, it is disconcerting that such a small proportion of patients received targeted therapy which has been associated with improved outcomes in a myriad of solid tumor indications. HER2 is overexpressed in 20–33% of EAC tumors, and EGFR is overexpressed in 25–30% of gastroesophageal tumors—demonstrating missed opportunities to potentially improve outcomes utilizing targeted therapies in our cohort (48, 49). Eight clinical trials testing EGFR targeted therapy with tyrosine kinase inhibitors (TKIs) vs chemotherapy in first-line non-small cell lung carcinoma demonstrated significant improvements in response rates and OS for every cohort treated with targeted therapy (50).…”

Section: Discussionmentioning

confidence: 96%

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

et al. 2017

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There has been an alarming rise in the incidence of esophageal adenocarcinoma which continues to have poor survival rates primarily due to lack of effective chemotherapy and presentation at advanced stages. Over a dozen chemotherapeutic agents are FDA approved for esophageal cancer (EC), and a two or three-drug combination is typically prescribed as first-line therapy for the majority of EC patients, administered either pre or post-operatively with esophageal resection. We have noticed significant variability in adjuvant and neoadjuvant regimens used in the community setting. The aim of this study was to review the various drug regimens used in the neoadjuvant setting for EC patients with adenocarcinoma undergoing resection at a single tertiary referral center in the Midwest. A total of 123 patients (stage II–III) underwent esophageal resection after neoadjuvant treatment at the center. Overall, 18 distinct drug regimens were used in 123 patients including two patients who received targeted therapy. Median survival post-surgery for this group was 11.2 months with no single regimen offering a survival advantage. These results reveal an unclear algorithm of how accepted regimens are prescribed in the community setting as well as a dire need for agents that are more effective. Additionally, it was noted that although proteomic markers have been found to predict drug response to 92% of the FDA-approved drugs in EC (12 of 13), according to pathology reports, molecular diagnostic testing was not used to direct treatment in this cohort. We therefore propose potential strategies to improve clinical outcomes including the use of a robust molecular oncology diagnostic panel and discuss the potential role for targeted chemotherapy and/or immunotherapy in the management of EC patients.

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Section: Discussionmentioning

confidence: 96%

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

et al. 2017

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“…Expression of HER2 is highly correlated with the prognosis of esophageal adenocarcinom [6], while the prognostic role in ESCC has hardly been investigated. We found that about 20 % of our patients were positive for HER2.…”

Section: Discussionmentioning

confidence: 99%

“…It is an important drug target for cancers, including breast cancer and gastroesophageal (GE) junction adenocarcinoma [6–7]. HER2 inhibition in combination with cisplatin-based chemotherapy has been demonstrated to significantly improve response rate and overall or progression-free survival in patients with adenocarcinoma of the gastro-esophageal junction or the stomach who over-express HER2 [7].…”

Section: Introductionmentioning

confidence: 99%

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

et al. 2016

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Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients.

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“…every 2 weeks. It is important to clarify that the use of trastuzumab as maintenance single agent beyond disease progression in the adjuvant or perioperative setting is not advised at this point outside of a clinical trial, and extrapolating data from the breast cancer literature and applying the same concepts in treating gastric and GEJ cancers is not recommended [86].…”

Section: Trastuzumabmentioning

confidence: 98%

From conventional chemotherapy to targeted therapy: use of monoclonal antibodies (moAbs) in gastrointestinal (GI) tumors

et al. 2014

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In recent years, significant progress has been made in the diagnosis and treatment of gastrointestinal cancers. Researches and clinicians however are still faced with challenges, not the least is the detection and management of tumors with varied gene mutation status. Clarification of the molecular pathology of gastrointestinal cancers may improve treatment options as well as quality of life and the long-term survival of this patient class. Therefore, molecular-targeted therapies have emerged as clinically useful drugs for gastrointestinal cancers cure, and predictive biomarkers have been heralded as the way to develop the right drug for the right patient. Moving from such appealing molecular background, we wrote an overview of the main targeted therapies, with particular interest to monoclonal antibodies that have already been approved in clinical practice or are being tested in gastrointestinal cancers treatment.

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Targeting the Human Epidermal Growth Factor Receptor 2 in Esophageal Cancer

Cited by 24 publications

References 26 publications

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

From conventional chemotherapy to targeted therapy: use of monoclonal antibodies (moAbs) in gastrointestinal (GI) tumors

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