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- Title
Relevance of Aberrations in Signal Transduction Pathways and Tumour Microenvironment in Colorectal Cancer for Cancer Precision Medicine.
- Authors
Wai Kien Yip; Boon Lee Chai; Wen Li Goh; Boon Yean Chai; Mohtarrudin, Norhafizah; Jabar, Mohd Faisal; Heng Fong Seow
- Abstract
Introduction: Cancer precision medicine is aimed for selecting treatments targeted to the needs of the individual patients based on the biomarker, genetic or phenotypic characteristics of the cancer cells. The ultimate aim is to improve clinical outcome and to minimize side effects. Current targeted therapies have arisen from decades of research on signal transduction pathways and major discoveries in immunology (Seow et al., OncoTargets and Therapy 2016,9: 2565-2574). It is well-documented that signalling pathways such as phosphoinositide 3-kinase (PI3K) and WNT are frequently deregulated pathways in several human cancers, including CRC and blockade of these pathways could potentially be useful for cancer therapy. One of the targeted drugs approved for metastatic colorectal cancer patients with wild type KRAS is cetuximab which targets the epidermal growth receptor (EGFR). KRAS mutations have been shown to be negative predictors of response to cetuximab. RAS and BRAF can acquire activating mutations, which render EGFR inhibitors ineffective. Methods: Thus, there is a need to screen for RAS and BRAF mutations before starting anti-EGFR therapy. One of the objectives of this talk is to provide an insight into the incidence of RAS, BRAF, PI3K and pTEN mutations (Yip WK et al., Acta Pathol Microbiol Immunol Scand (APMIS), 2013, 121: 954-66). Results: In addition, we have also determined the relationship between biomolecules of the WNT and Notch signalling pathways by immunohistochemical staining, the effects of small chemical inhibitors and antisense strategies by using inhibitors of microRNAs on cancer cell growth and angiogenesis. The tumour microenvironment can influence tumour growth and progression, and metastasis. The phenotypes of macrophage in primary CRC can be detected by immunohistochemistry and molecular interactions following interaction between M1 and M2-like macrophages and cancer stem-like cells are currently under investigation. Conclusion: These approaches provide insights into the molecular alterations in cancer and may assist in the development of new strategies for treatment of cancer.
- Subjects
CELLULAR signal transduction; INDIVIDUALIZED medicine; COLORECTAL cancer; NOTCH signaling pathway; TUMORS; BIOMOLECULE analysis; CANCER cell growth
- Publication
Malaysian Journal of Medicine & Health Sciences, 2017, Vol 13, p13
- ISSN
1675-8544
- Publication type
Article