Therapeutic Approaches for Metastases from Colorectal Cancer and Pancreatic Ductal Carcinoma

Abstract

Metastasis is the process of dissemination of a tumor, whereby cells from the primary site dislodge and find their way to other tissues where secondary tumors establish. Metastasis is the primary cause of death related to cancer. This process warrants changes in original tumoral cells and their microenvironment to establish a metastatic niche. Traditionally, cancer therapy has focused on metastasis prevention by systematic treatments or direct surgical re-sectioning. However, metastasis can still occur. More recently, new therapies direct their attention to targeting cancer stem cells. As they propose, these cells could be the orchestrators of the metastatic niche. In this review, we describe conventional and novel developments in cancer therapeutics for liver and lung metastasis. We further discuss the resistance mechanisms of targeted therapy, the advantages, and disadvantages of diverse treatment approaches, and future novel strategies to enhance cancer prognosis.

Keywords: cancer stem cells; cancer treatments and progression biomarkers; liver metastasis; lung metastasis.

Figure 1

Liver metastases process. Development of liver metastases involves changes in tumor cell metabolism, as well as EMT and is induced by inflammatory cytokines, miRNAs, hypoxia, and pH. These factors allow for dissemination of CSC. Growth factors promote survival of cells in the blood and the lymphatic circulation, these cells form clusters (fibroblasts, endothelial, tumor-infiltrated myeloid cells, or pericytes) in order to arrive to hepatic tissue. Also, liver metastasis niche is improved by damage inducers, that activate HSCs, KCs, CAFs, myofibroblast, TAMs or produce oxidative stress and cytokines production promoting CSC establishment and growth.

Figure 2

Lung metastases process. Tumor cell dissemination to lungs results after tissue damage that induces local inflammation and improves metastatic environment. club cells, alveolar cells recruit neutrophils, CAFs, TAMs, MSCs, and form a protective niche for help to CSC. In addition, metastases are promoted by CXCR4 signaling, miRNAs, growth factors, hypoxia, pH and glucose metabolism. Deposition of tenascin-C, collagen I, fibronectin and particular metalloproteases 2 and 9 after cancer cells dissemination to the lung in and important feature for CSC and tumor outgrowth.