Challenges and limitations of targeting cancer stem cells and/or the tumour microenvironment

The existence of cancer cells with stem cell properties (Cancer Stem Cells, CSCs) and their association with tumor resistance and relapse has led to the search for active compounds to eliminate these cells or modulate their stemness in the hope of curing cancer. So far, three classes of drugs that target cancer stemness (Stemness Modulator Drugs) have been identified: i) drugs that selectively eliminate CSCs (stem cell targeting drugs); ii) drugs that decrease stemness (stemness inhibitor drugs); and iii) drugs that promote stemness (stemness promoting drugs). In addition, microenvironment modulating drugs aimed at selectively targeting the stem cell niche are being investigated and may represent an important class of drug for cancer therapy. This article will briefly review the current use of these substances and discuss the potential outcomes, challenges and limitations of treatment modalities using these classes of drugs for cancer treatment. Finally, a modular tumor model will be proposed as a guide to integrate our knowledge on the biology of cancer stem cell with that of the tumor microenvironment to promote a more rational development of anticancer therapy.