Targeted therapies in colorectal cancer—an integrative view by PPPM

Abstract

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches.

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

“…However, it later proved ineffectual in this and several other randomized phase III studies (Dahan et al, 2009;Hagan et al, 2013;Klingbiel et al, 2015;Saltz et al, 2007;Taieb et al, 2014). Therefore, irinotecan is not used in the adjuvant setting in CRC patients.…”

“…It accounts for approximately 50,000 deaths each year in the United States (Siegel et al, 2012;Winawer et al, 2003). The reduction in death rates for CRC reflects improvements in earlier cancer detection and management, in combination with an increased understanding of the molecular and genetic basis of the disease (Hagan et al, 2013). It is now apparent that CRC is a heterogeneous disease characterised by a number of molecular subtypes .…”

Epithelial-mesenchymal transition-associated microRNAs in colorectal cancer and drug-targeted therapies (Review)

“…The epidermal growth factor receptor (EgFR) is known to be overexpressed in CRC EMT, while anti-EgFR therapy is considered effective. Tyrosine kinase inhibitors (TKIs), such as sorafenib and gefitinib, were designed to block the cascade of reactions which are crucial to tumor development and survival (132). Sorafenib is currently being tested in phase II trials of CRC.…”

“…The two antibodies prevent EgFR auto-phosphorylation by binding to the extracellular domain. They also inhibit activation of the MAPK and P13K downstream cell signaling pathways (132). In addition, the two drugs exhibited significant antitumor activity, although limitations and side effects were observed (134)(135)(136)(137).…”

CYTOTOXICITY AND MODE OF CELL DEATH INDUCED BY TRIPHENYLTIN (IV) COMPOUNDS <i>IN VITRO</i>

“…Therefore, the effective ways to combat the disease, specifically colorectal cancerare crucially needed and many researchers are currently paying a great attention into this matter. The current treatment used forcolorectal cancers are surgery, chemotherapy, radiation therapy and targeted therapies (Hagan et al, 2013). Taken together, surgery excision remains as a basis for cancer treatment especially at the early stages of colorectal cancer (Hagan et al, 2013).…”