Gene heterogeneity in metastasis of colorectal cancer to the lung

Colorectal cancer (CRC) as a heterogeneous disease, is one of the most common and serious cancers with high metastases and mortality. Lung is one of the most common sites of CRC metastases with high heterogeneity between cells, pathways, or molecules. The present review will focus on potential roles of gene heterogeneity in KRAS pathway in the development of CRC metastasis to lung and clinical therapies, which would lead to better understanding of the metastatic control and benefit to the treatment of metastases. KRAS is the central relay for pathways originating at the epidermal growth factor receptor (EGFR) family. KRAS mutation exists in about 40% CRC, associated with higher cumulative incidence of CRC lung metastasis, and acts as an independent predictor of metastasis to lung. Mutations in KRAS can lead to poor response of patients to panitumumab, and inferior progression-free survival. However, most patients with KRAS wild-type tumors still do not respond, which indicates other mutations. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation was associated with lung metastases in metastatic colorectal cancer. PIK3CA mutation in exon 20 was found to be correlated with patient survival in the metastatic setting after the treatment with cetuximab and chemotherapy. The heterogeneity of KRAS pathway was found in the phosphatase and tensin homologue deleted on chromosome ten loss, disheveled binding antagonist of beta catenin 2 overexpression and increased dual-specificity protein phosphatase 4 expression of CRC lung metastasis.