<p>Colorectal Cancer Genetics, Incidence and Risk Factors: In Search for Targeted Therapies</p>

Abstract

Each year, colorectal cancers (CRCs) affect over a quarter of a million people. The risk of developing CRC in industrialized nations is approximately 5%. When the disease is localised, treatment success rates range from 70-90%; however, advanced CRC has a high mortality rate, consistently ranking in the top three causes of cancer-related deaths. There is a large geographic difference in global distribution, and CRC is predominantly associated with developed countries and a Western lifestyle and diet. As such, the developed world accounts for more than 63% of all cases of CRC. Geographic variations also predict cancer outcomes, which differ between racial and ethnic groups. This variation is due to inequalities in wealth, differences in the exposure to risk factors and barriers to high-quality cancer prevention, early detection and treatment. The aim of this paper was to review CRC in lowand middle-income countries such as South Africa, India, Brazil and China, and compare them with high-income countries such as the United States of America and the United Kingdom. It is important to note that these economically less developed countries, with historically low CRC rates, are experiencing an increased frequency of CRC. The review also discusses biological markers and genetic pathways involved in the development of colorectal cancer. Genes known to be responsible for the most common forms of inherited CRCs have also been identified but more remain to be identified. This would provide more candidate genes to be added to known biomarkers. CRC burden can be controlled through the widespread application of existing knowledge, such as reduced smoking habits, vaccination, early detection and promoting physical activity, accompanied by a healthy diet. An increased understanding of the molecular mechanisms and events underlying colorectal carcinogenesis will enable the development of new targets and therapeutic drugs.

Subcellular distribution of ezrin/radixin/moesin and their roles in the cell surface localization and transport function of P-glycoprotein in human colon adenocarcinoma LS180 cells

“…Colorectal cancer (CRC) is the second leading cause of cancer deaths among males and females combined [1]. Despite great advances in the treatment of cancer in the last few decades, effective strategies for pharmacotherapy of CRC are still under development [2][3][4]. One of the major problems with the treatment of CRC is the acquired multidrug resistance (MDR) of cancer cells, not only to a broad spectrum of structurally and functionally distinct conventional chemotherapeutic drugs but also to molecular targeted drugs during the course of their treatment [5][6][7][8][9][10].…”

Role of Ezrin/Radixin/Moesin in the Surface Localization of Programmed Cell Death Ligand-1 in Human Colon Adenocarcinoma LS180 Cells

“…In addition to the high morbidity and mortality in CRC, it appears to be difficult to further advance traditional treatment options, such as surgery, chemotherapy, and radiotherapy [ 2 ]. Hence, there is a need to develop new treatment methods to improve the poor prognosis in patients with CRC [ 3 , 4 , 5 , 6 ].…”

Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)

“…In 2020, ~1,1 million new CRC cases were reported along with 576,858 deaths, accounting for nearly 10.0% of new cases and 5.8% of all cancer-associated deaths globally ( 1 ). While up to 10-15% of CRC patients carry one or more inherited pathogenic mutations associated with inherited syndromes (such as familial adenomatous polyposis or hereditary non-polyposis CRC) ( 3 ), 85% of CRC cases are sporadic and attributable to risk factors including age, race and sex, as well as modifiable risk factors including diet, tobacco use, diabetes and obesity ( 4 ). In the US, it is estimated that ~20% of newly diagnosed CRC patients have metastatic disease (mCRC) at the time of presentation ( 2 ), of which 3-5% harbor high microsatellite instability (MSI-H) and deficiency in mismatch repair mechanism (dMMR) of their genome ( 5 , 6 ).…”