Targeted therapy for colorectal cancer resistance to EGF receptor antibodies and new trends

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Publisher: Expert Reviews Ltd.
Document Type: Report
Length: 2,578 words
Lexile Measure: 1450L

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Author(s): Christos Katsios 1 , Denosthenes E Ziogas 2 , Dimitrios H Roukos 3 , George Baltogiannis 4

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biomarkers; colorectal cancer; drugs; EGFR; genomic landscape; resistance; Wnt

Colorectal cancer (CRC) remains a major health problem worldwide despite substantial advances in multimodal treatment. High quality comparative-effectiveness research has standardized surgery, radiotherapy and systemic chemotherapy. But there is still controversy on the selection of the best chemotherapeutic regimen and tailored targeted therapy. For example, there is currently a debate on whether testing for microsatellite instability and/or for the multigene assays, ColoPrint and Oncotype Dx, should be used for adjuvant chemotherapy decision in localized CRC. In the metastatic setting, decisions on cetuximab versus panitumumab for patients with KRAS wild-type (wt) metastatic CRC (mCRC) has become complex as the survival benefit provided by these anti-EGF receptor (EGFR) antibodies has not been clear. Here we summarize the latest results and the new changes in biomedical research that include applying high-throughput (HT) sequencing and array technologies to reach robust biomarkers and more effective drug combinations.

Standardizing prevention & treatment

Diagnostics, prevention and treatment of patients with CRC have improved over recent decades. Colonoscopy screening in people over 50 years of age improves overall survival (OS) by identifying preneoplastic lesions or tumors at an early stage. Genetic testing in individuals with a significant family history of CRC can identify the carriers of driver mutations in mismatch-repair genes (MSH2, MLH1, MSH6 and PMS2 ) and therefore those who are at very high-risk of developing hereditary nonpolyposis CRC. Because genetic testing is expensive, microsatellite instability and immunochemistry for overexpression of these genes can increase the accuracy of selected patients for genetic testing, thereby reducing costs. Although patients with hereditary nonpolyposis CRC account for less than 5% of all CRC cases, effective risk-reducing surgery and/or surveillance with colonoscopy can save the lives of these high-risk individuals [101] .

In patients with histologically confirmed adenocarcinoma, pre-treatment staging is essential because it defines the plan of therapeutic strategy. For example, patients with locally advanced CRC can benefit more from a preoperative, also called neoadjuvant, treatment than the traditional postoperative treatment, while detection of resectable liver or lung metastases can modify the entire therapeutic approach.

Surgery aims for complete resection of the tumor (R0), which can also be performed with minimally invasive laparoscopic techniques, improving short-term quality of life but not OS. For resectable stage II and III colon tumors, surgical resection and adjuvant chemotherapy is the standard approach. For rectal cancer, adjuvant chemoradiotherapy is used either in the postoperative setting for resectable tumors, or as neoadjuvant treatment for locally advanced disease. In metastatic stage IV with completely resectable (R0) liver or lung metastases in primary diagnosis or after neoadjuvant treatment surgery, systemic chemotherapy is recommended by the National Comprehensive Cancer Network similar to the treatment of stage III disease [101] .

Targeted therapy

The field of targeted therapy provides exciting opportunities for improving oncological outcomes. Over the last decade it has evolved exponentially and the list of approved drugs is rapidly growing. Drugs targeting mutated or...

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Gale Document Number: GALE|A312892144