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Colorectal Cancer:

DKN-01 + bevacizumab
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Colorectal cancer overview

Colorectal cancer is the third most frequent cancer globally and the second leading cause of death. According to the WHO, there were nearly 2 million new cases of colorectal cancer in 2020, with nearly 1 million deaths. Colorectal cancer includes colon cancer (57.5%), rectal cancers (35%), and anal cancer (2.5%). When the symptoms of CRC appear, such as rectal bleeding, anemia, or abdominal pain, most patients are already in the advanced stage where cancers are aggressive, malignant, and metastatic.

Colorectal cancer is classified today into four consensus molecular subtypes (CMSs)

CMS1, representing 14% of CRC, is usually a right-sided (proximal) colon cancer and is characterized by microsatellite instability, hypermutations, BRAF mutations, and immune infiltration.

CMS2, representing 37% of CRC, is mainly left-sided (distal colon cancer) and characterized by activation of Wnt and Myc signaling pathways. High expression of β-catenin in CMS2 is associated with poor prognosis and CRC progression.

CMS3, representing 13% of CRC, is characterized by KRAS mutation, constitutive activation of MAPK pathway, and metabolic dysregulation.

CMS4, representing 23% of CRC, although commonly left-sided, is characterized by extensive stromal invasion, angiogenesis and upregulation of genes related to epithelial mesenchymal transition.

The global number of new CRC cases is predicted to reach over 3 million in 2040, based on the projection of aging, population growth, and human development. The increase in CRC incidence is mainly attributed to the elevated exposure to environmental risk factors resulting from shifting lifestyle and diet.