Targeting cancer-initiating cell drug-resistance: a roadmap to a new-generation of cancer therapies?

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The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of ‘cancer-initiating cells’ able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer initiating cells display a range of self-defense systems that include almost all mechanisms of drug resistance. Different molecular pathways and markers, identified in this malignant sub-population, are becoming targets for novel compounds and for monoclonal antibodies, which may be combined with conventional drugs. These interventions might eliminate drug-resistant cancer-initiating cells and lead to remission or cure of cancer patients.

Angela Alama, Anna Maria Orengo, Silvano Ferriniand Rosaria Gangemibriefly review different approaches to override the drug-resistance mechanisms of cancer initiating cells (CICs) and for increasing the efficacy of current cytotoxic treatments. They focus our attention to the new anti-CICs based therapies that have entered clinical trials. In addition, they discuss the possible role of CICs in tumor immune-escape as well as their targeting by immunotherapy strategies.

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