Aggressive cancers

Cancer-related diseases are within the top three causes of death worldwide. Although for some cancer types the survival rate has greatly improved during the last years due to advances in diagnostic and therapeutic approaches, several highly aggressive cancers remain as unmet clinical needs. These aggressive tumors share common features such as high chemoresistance to conventional systemic therapies, rapid relapse after treatment and metastases formation in vital organs which, eventually, leads to death. These features are often attributed to specific subpopulations of malignant cells with tumor- and metastasis-initiating properties, such as cancer stem cells (CSCs). Indeed, it has become apparent that cancer cells within a tumor are very heterogeneous: not only genetic and epigenetically, but also in terms of differentiation state and functionality. Numerous microenvironmental and cell-autonomous factors support and amplify such heterogeneity, contributing to cancer malignancy by inducing stemness and the acquisition of pro-metastatic abilities.

Due to its crucial role in chemoresistance, tumor relapse and metastasis, a great number of research projects are currently underway trying to find and target both external and internal signals regulating the functionality of cancer and metastasis-initiating cells. Due to its intrinsic similarities with normal adult stem cells, the scientific community from the cancer stemness and metastasis field faces a great challenge: the identification or design of therapeutic strategies able to specifically target tumoral stem cells maintaining the normal stem cells pool unharmed. To do so, the study of the tumor microenvironment (or CSC niche specifically affecting these cells), has become an essential tool due to its particularities: on one side, the fundamental properties of certain tumors, such as hypoxia and lack of nutrients due to the hypervascularization and desmoplasia; on the other side, the unique features conferred by tumoral stromal cells, including endothelial cells and different populations of fibroblasts and immune cells.

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Allied Journal of Medical Research
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