Treatment in advanced colorectal cancer: what, when and how?

Abstract

Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC.

Clinicopathological significance of prolactin receptor expression in colorectal carcinoma and corresponding metastases

“…[4][5][6] The introduction of new drugs, the so-called biologicals, which selectively target pathways implicated in tumor growth and development, such as epidermal growth factor receptor or vascular endothelial growth factor antagonists, has further improved outcome of affected patients. [7][8][9] The role of human prolactin and its receptor, the prolactin receptor, in cancer has been analyzed for almost two decades. Prolactin receptor is expressed in various extrapituitary cells, including breast, liver, pancreas, and gastrointestinal tissues.…”

Fibroblast Growth Factor Receptor 2 IIIc as a Therapeutic Target for Colorectal Cancer Cells

“…The prognosis of colorectal carcinoma remains unfavorable when the disease has progressed to the unresectable stage; thus, new therapeutic strategies for advanced colorectal carcinomas, such as molecular-targeted agents, are a high priority (1). Colorectal tumorigenesis is thought to be a multistep process involving the accumulation of genetic alterations and the well-characterized molecular events of the adenoma-to-carcinoma sequence (2).…”

Oncogenic KRAS sensitises colorectal tumour cells to chemotherapy by p53-dependent induction of Noxa

“…Chemotherapy of colorectal cancer mainly involves the fluoropyrimidine drug 5-fluorouracil (5-FU) and the platinum drug oxaliplatin (Chau and Cunningham, 2009). The response of colorectal tumours to these compounds is determined both by the genetic background of tumour cells as well as by environmental cues.…”