Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?

Department of Surgical and Oncological Sciences, Section of Medical Oncology, University of Palermo, Via del Vespro 127, Palermo, Italy.
Cancer Treatment Reviews (Impact Factor: 6.02). 11/2010; 36 Suppl 3:S56-61. DOI: 10.1016/S0305-7372(10)70021-9
Source: PubMed

ABSTRACT An important molecular target for metastatic CRC treatment is the epidermal growth factor receptor (EGFR). Many potential biomarkers predictive of response to anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have been retrospectively evaluated, including EGFR activation markers and EGFR ligands activation markers. With regard to the "negative predictive factors" responsible for primary or intrinsic resistance to anti-EGFR antibodies a lot of data are now available. Among these, KRAS mutations have emerged as a major predictor of resistance to panitumumab or cetuximab in the clinical setting and several studies of patients receiving first and subsequent lines of treatment have shown that those with tumors carrying KRAS mutations do not respond to EGFR-targeted monoclonal antibodies or show any survival benefit from such treatments. The role of B-RAF mutations, mutually exclusive with KRAS mutations, in predicting resistance to anti-EGFR mAbs is not yet consolidated. It therefore appears that BRAF mutations may play a strong negative prognostic role and only a slight role in resistance to anti-EGFR Abs.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Since a chance for cure was found out in metastatic colorectal cancer (mCRC) patients undergoing a resection of liver and lung metastases, high tumor shrinkage by chemotherapy regimens and their combination with targeted agents have been addressed in potentially resectable mCRC. However, most mCRC patients cannot reach this opportunity because of tumor burden or metastatic sites. For these patients a salvage systemic therapy could be offered to prolong survival. To date, a huge number of clinical trials provided some evidences for the achievement of this goal. A lot of chemotherapeutic regimens in combination with biological therapies are now available. We tried to propose a simple way to choose the best options and to plan an optimal sequence of treatments. This tool could help the oncologists worldwide to better and easily manage mCRC patients who need salvage systemic therapy.
    Expert opinion on biological therapy 03/2014; · 3.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of death globally. Significant improvements in survival have been made in patient with metastasis by new therapies. For example, Cetuximab and Panitumumab are monoclonal antibodies that inhibit the epidermal growth receptor (EGFR). KRAS mutations in codon 12 and 13 are the recognized biomarkers that are analyzed in clinics before the administration of anti-EGFR therapy. Genetic analyses have revealed that mutations in KRAS predict a lack of response to Panitumumab and Cetuximab in patients with metastatic CRC (mCRC). Notably, it is estimated that 35-45% of CRC patients harbor KRAS mutations. Therefore, KRAS mutation testing should be performed in all individuals with the advanced CRC in order to identify the patients' who will not respond to the monoclonal EGFR antibody inhibitors. New techniques for KRAS testing have arisen rapidly, and each technique has advantages and disadvantages. Herein, we review the latest published literature specific to KRAS mutation testing techniques. Since reliability and feasibility are important issues in clinical analyses. Therefore, this review also summarizes the effectiveness and limitations of numerous KRAS mutation testing techniques.
    Clinica chimica acta; international journal of clinical chemistry 02/2014; · 2.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is one of the most common human malignant diseases and the second leading cause of cancer-related deaths worldwide. The treatment of advanced CRC has improved significantly in recent years. With the emergence of two targeted antibodies, cetuximab (Erbitux), an anti-epidermal growth factor receptor monoclonal antibody and bevacizumab (Avastin), a vascular endothelial growth factor monoclonal antibody, the treatment of metastatic CRC has entered the era of personalized therapy. Predictive and prognostic biomarkers have, and will continue to, facilitate the selection of suitable patients and the personalization of treatment for metastatic CRC (mCRC). In this review, we will focus primarily on the important progresses made in the personalized treatment of mCRC and discuss the potentially novel predictive and prognostic biomarkers for improved selection of patients for anti-cancer treatment in the future.
    World Journal of Gastroenterology 04/2014; 20(14):3858-3874. · 2.55 Impact Factor


Available from
May 26, 2014