Targeting cancer stem cells to suppress acquired chemotherapy resistance

Abstract

Acquired resistance has curtailed cancer survival since the dawn of the chemotherapy age more than half a century ago. Although the application of stem cell (SC) concepts to cancer captured the imagination of scientists for many years, only the last decade has yielded substantial evidence that cancer SCs (CSCs) contribute to chemotherapy resistance. Recent studies suggest that the functional and molecular properties of CSCs constitute therapeutic opportunities to improve the efficacy of chemotherapy. Here we review how these properties have stimulated combination strategies that suppress acquired resistance across a spectrum of malignancies. The clinical implementation of these strategies promises to rejuvenate the effort against an enduring challenge.

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…Cancer stem cells (CSCs) are an attractive target for combination therapy as well, since CSCs reside within specific niches and contribute to tumor relapse and drug resistance [136,137]. Various CSC properties such as metabolism, TME interactions, epigenetic states, quiescence, self-renewal, lack of differentiation, quiescence, and deregulation of apoptotic/survival pathways have been exploited to synergistically enhance chemotherapy through combination therapy [138]. For example, targeting the developmental pathway associated with tumor type pathogenesis, Hedgehog pathway, boosted efficacy of TKI inhibitor Imatinib while increasing survival time in a chronic myeloid leukemia murine model [139].…”

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

“…The mice were subcutaneously injected at the right axillary space with 0.1 mL of cell suspension containing 1×10 6 CT-26 cells. After cell inoculation, a solid tumor was allowed to grow $100 mm 3 . After 1 week, mice were divided into nine groups (six mice per group): 1) 5% glucose solution (Control); 2) Blank-LEs; 3) OXA-Sol; 4) IRI-Sol; 5) OXALEs; 6) IRI-LEs; 7) OXA/IRI-Sol; 8) OXA-LEs/IRI-LEs and 9) OXA/IRI-LEs.…”

“…The mice were subcutaneously injected at the right axillary space with 0.1 mL of cell suspension containing 1×10 6 CT-26 cells. When the tumor volume reached 200-300 mm 3 , mice were injected with 1) DiI and DiO mixture solution, 2) mixture of DiI-LEs and DiO-LEs and 3) DiI/DiO co-loaded LEs. The administration concentration for both DiI and DiO was 125 µg/ mL.…”

“…1 Combination chemotherapy is widely employed in clinics, 2,3 with the objective of improving therapeutic effect and decreasing drug resistance, by targeting a single oncogenic pathway through different modes of action or across multiple interrelated pathways. [4][5][6] Taking into account that the traditional administration in clinics is just a simple cocktail, the uncoordinated pharmacokinetics and uncontrolled release properties of different drugs restrict their applications, leading to the uncertainty of treatment.…”

STAT3 inhibitor enhances chemotherapy drug efficacy by modulating mucin 1 expression in non-small cell lung carcinoma

“…Stemness in cancer cell populations is widely implicated for facilitating the chemoresistance. Stemness in cancer cell population is widely implicated for facilitating the chemoresistance [7][8][9][10]. Developing tailor-made chemotherapeutic options based on cancer subtypes and the underlying facilitating mechanism for the chemoresistance has been proposed as an alternate strategy to improve outcomes [11].…”