Progression to Metastasis of Solid Cancer

Abstract

Metastatic dissemination of cancer cells, their colonization at distal sites, and ultimate disruption of tissue physiology are the root causes of most deaths from solid cancers, particularly in tumor types where the primary lesion can be easily dissected and discarded [...]

Copy Number Variations as Determinants of Colorectal Tumor Progression in Liquid Biopsies

“…Metastasis involves several distinct steps whereby the tumor cells travel through the circulation to implant and grow at secondary tissue sites. These steps involve local invasion, epithelial–mesenchymal transition (EMT), cell migration, intravasation into the lymphatic or hematogenous system, the survival of the tumor cell in the vascular system, the extravasation from the vasculature to distal tissue and colonization to secondary organs [ 32 , 33 ]. At the time of diagnosis, 20% of CRC patients already have metastases, with the liver being the most common site of metastasis (70%), followed by the thorax (32%), peritoneum (21%) and, in some instances, metastasis can also occur to the lungs, nervous system, skin and soft tissue [ 34 ].…”

Modeling the Role of Cancer-Associated Fibroblasts in Tumor Cell Invasion

“…Studies have demonstrated that these cells at the metastatic site express epithelial markers such as E-cadherin, suggesting they have gone through the reverse process of the mesenchymal-to-epithelial transition (MET) in this last step of the cascade. Altogether, this forms what is known as the EMT/MET model of metastatic dissemination [ 6 , 7 ]. This model in itself continues to be challenged and updated with new experimental evidence; while both are important, EMT and MET may not be necessary nor sufficient for the onset of metastasis, and the extent of their contribution varies widely with disease context.…”

Thinking (Metastasis) outside the (Primary Tumor) Box

“…The metastasis of tumor cells into vital organs is a major cause of death from diverse types of malignancies [1][2][3][4]. One model posits that metastasis is driven by the same oncogenic drivers that promote primary lesions [5] (reviewed in [3]).…”

“…The metastasis of tumor cells into vital organs is a major cause of death from diverse types of malignancies [1][2][3][4]. One model posits that metastasis is driven by the same oncogenic drivers that promote primary lesions [5] (reviewed in [3]). This model is supported by the high concordance between the oncogenic landscapes of metastases versus primary lesions from the same patients [6].…”

“…We envisage that primary-enriched oncogenic drivers evolve to promote clonal competition and expansion at the local site. Such drivers may not be compatible with, and may even oppose, the metastatic cascade; therefore, their activity is diminished in metastases [1][2][3][4]. For example, a glycolytic shift facilitates the efficient synthesis of macromolecules required for rapid cell duplication [44,45], yet oxidative phosphorylation (OX-PHOS) is a hallmark of circulating, metastatic tumor cells [3,23,46,47].…”