Approaches for targeting cancer stem cells drug resistance

ABSTRACT

Introduction: Several reports have suggested that a population of undifferentiated cells known as cancer stem cells (CSCs), is responsible for cancer formation and maintenance. In the last decade, the presence of CSCs in solid cancers have been reported.

Areas covered: This review summarizes the main approaches for targeting CSCs drug resistance. It is indeed known that CSCs may contribute to resistance to conventional chemotherapy, radiotherapy and targeted agents. Among the mechanisms by which CSCs escape anticancer therapies, removal of therapeutic agents by drug efflux pumps, enhanced DNA damage repair, activation of mitogenic/anti-apoptotic pathways; the main features of CSCs, stemness and EMT, are involved, as well as the capability to evade immune response.

Expert opinion: Different approaches are suitable to target CSCs mediated drug resistance. Some of them are currently under clinical evaluation in different cancer types. A better understanding of CSC biology, as well as more accurate study design, may maximize the therapeutic effects of these agents. In this respect, it is important to establish: (i) which molecules should be targeted; (ii) what drug combinations may be suitable; (iii) which patient settings will CSC targeting offer the highest clinical benefit; and (iv) how to integrate therapeutic approaches targeting CSCs with standard cancer therapy.

KEYWORDS:

• Cancer stem cells
• resistance
• stemness
• EMT
• immune evasion

Article highlights

• Cancer stem cells (CSCs) represents a population of undifferentiated cells responsible for cancer formation and maintenance.

• CSCs may contribute to resistance to conventional chemotherapy, radiotherapy and targeted agents.

• The main features of CSCs, stemness and EMT, as well as the capability to evade immune response, are involved in the onset of resistance to anticancer therapies.

• Approaches targeting: (A) canonical proliferative pathways, (B) the stemness signaling pathways, (C) EMT signaling pathways and (D) immune surveillance evasion are under clinical evaluation to prevent or overcome CSCs mediated drug resistance.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) Investigator Grant 2015-2017 (IG-15388) to R Bianco. This study was also supported by the Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO).