Abstract
Cancers are heterogeneous at the cell level, and the mechanisms leading to cancer heterogeneity could be clonal evolution or cancer stem cells. Cancer stem cells are resistant to most anti-cancer treatments and could be preferential targets to reverse this resistance, either targeting stemness pathways or cancer stem cell surface markers. Gold nanoparticles have emerged as innovative tools, particularly for photo-thermal therapy since they can be excited by laser to induce hyperthermia. Gold nanoparticles can be functionalized with antibodies to specifically target cancer stem cells. Preclinical studies using photo-thermal therapy have demonstrated the feasibility of targeting chemo-resistant cancer cells to reverse clinical chemoresistance. Here, we review the data linking cancer stem cells and chemoresistance and discuss the way to target them to reverse resistance. We particularly focus on the use of functionalized gold nanoparticles in the treatment of chemo-resistant metastatic cancers.
Highlights
Cancer heterogeneity was demonstrated on clear-cell renal-cell carcinoma, using whole-genome analyses of multiple samples from the same primary tumor [1,2]
Cancer stem cells located at the invasive front of a tumor, contrary to quiescent cancer stem cells, have invasive and metastatic capabilities linked to an epithelial-to-mesenchymal transition phenotype [51]
On cancer samples from patients with metastatic renal cell carcinoma, we showed that the numbers of cancer stem cells increased after treatment with sunitinib, but only in peri-necrotic hypoxic areas [6]
Summary
Cancer heterogeneity was demonstrated on clear-cell renal-cell carcinoma, using whole-genome analyses of multiple samples from the same primary tumor [1,2]. Secondary resistances almost constantly occur, and cancer stem cells are suggested as a potential source of this chemoresistance which has an increased risk of metastases and a lower survival rate [4,5,6,7,8]. In this narrative review, we analyze the recent literature on the role of cancer stem cells in chemoresistance to anti-cancer agents. We provide a synthesis on how to target these cancer stem cells to reverse chemoresistance, for translational purposes
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