Combining epidermal growth factor receptor inhibitors and radiation therapy in pancreatic cancer: Small step or giant leap?

JOP: Journal of the pancreas 02/2009; 10(3):231-6.
Source: PubMed


Targeting the epidermal growth factor receptor (EGFR) with small molecule inhibitors or monoclonal antibodies in combination with chemotherapy and radiation is a theoretically appealing strategy in pancreatic cancer. EGFR inhibitors have shown efficacy as radiosensitizers and activity against metastatic pancreatic cancer when combined with gemcitabine. This paper examines the available clinical data, with a focus on locally advanced, unresectable disease. Further studies with a focus on understanding the basic biology of EGFR inhibition are needed to identify an optimal multi-modality regimen.

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Available from: Muhammad Wasif Saif,
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    ABSTRACT: Importance of the field: KRAS mutation is the most common oncogenic alteration in various human cancers. Recently, KRAS has emerged as an important predictive biomarker in common malignancies such as metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC). This work aims to discuss the clinical impact of the KRAS mutation status on state-of-the-art treatment approaches, including epidermal growth factor receptor (EGFR)-targeted therapies. Areas covered in this review: This review considers the potential of KRAS to serve as a diagnostic, prognostic or predictive biomarker in various cancers, including those of the lung, colon/rectum, pancreas, ovary and endometrium. What the reader will gain: KRAS mutations in mCRC and NSCLC primary tumors predict resistance to EGFR-targeted therapy. In pancreatic cancer, KRAS may prove useful as a diagnostic biomarker to screen for early neoplasia. Furthermore, quantitative KRAS mutation analysis could have the potential to distinguish pancreatic cancer from other conditions such as chronic pancreatitis. With respect to ovarian and endometrial cancer, further studies should focus on determining reliable biomarkers for predicting response to EGFR-targeted therapy. Besides EGFR inhibition, KRAS may also serve as a diagnostic and predictive biomarker for evolving therapies directed against mutant RAS proteins. Take home message: KRAS has been recognized as an outstanding predictive biomarker to select mCRC and NSCLC patients for EGFR-targeted therapies; however, multi-determinant approaches including other molecular markers should facilitate the identification of patients likely to respond to such therapies.
    Expert Opinion on Medical Diagnostics 09/2010; 4(5):383-95. DOI:10.1517/17530059.2010.510512
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