Targeting Cancer Stem Cells to Overcome Chemoresistance

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 182

Record: found
Abstract: found
Article: not found

Identification of pancreatic cancer stem cells.

Chenwei Li, David G Heidt, Piero Dalerba … (2007)

Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Although data have been provided to support this theory in human blood, brain, and breast cancers, the identity of pancreatic cancer stem cells has not been determined. Using a xenograft model in which primary human pancreatic adenocarcinomas were grown in immunocompromised mice, we identified a highly tumorigenic subpopulation of pancreatic cancer cells expressing the cell surface markers CD44, CD24, and epithelial-specific antigen (ESA). Pancreatic cancer cells with the CD44(+)CD24(+)ESA(+) phenotype (0.2-0.8% of pancreatic cancer cells) had a 100-fold increased tumorigenic potential compared with nontumorigenic cancer cells, with 50% of animals injected with as few as 100 CD44(+)CD24(+)ESA(+) cells forming tumors that were histologically indistinguishable from the human tumors from which they originated. The enhanced ability of CD44(+)CD24(+)ESA(+) pancreatic cancer cells to form tumors was confirmed in an orthotopic pancreatic tail injection model. The CD44(+)CD24(+)ESA(+) pancreatic cancer cells showed the stem cell properties of self-renewal, the ability to produce differentiated progeny, and increased expression of the developmental signaling molecule sonic hedgehog. Identification of pancreatic cancer stem cells and further elucidation of the signaling pathways that regulate their growth and survival may provide novel therapeutic approaches to treat pancreatic cancer, which is notoriously resistant to standard chemotherapy and radiation.

0 comments Cited 875 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

CD44: from adhesion molecules to signalling regulators.

Helmut Ponta, Larry Sherman, Peter A Herrlich (2003)

Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades. The CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes--not only by establishing specific transmembrane complexes, but also by organizing signalling cascades through association with the actin cytoskeleton. CD44 and its associated partner proteins monitor changes in the extracellular matrix that influence cell growth, survival and differentiation.

0 comments Cited 588 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

William Gradishar, Sergei Tjulandin, Neville Davidson … (2005)

ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil-based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel. Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m(2) intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m(2) intravenously with premedication (n = 225). ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time. ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.

0 comments Cited 434 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 13 December 2018

Publication date Collection: December 2018

Volume: 19

Issue: 12

Electronic Location Identifier: 4036

Affiliations

[1 ]Institut National de la Santé et de la Recherche Médicale (INSERM), U1165, F-75010 Paris, France; toni.nunes@ 123456outlook.fr (T.N.); diaddin_h@ 123456hotmail.com (D.H.); christophe.leboeuf@ 123456univ-paris-diderot.fr (C.L.); morad.elbou@ 123456gmail.com (M.E.B.); guillaume.gapihan@ 123456gmail.com (G.G.); thuylinh.nong@ 123456gmail.com (T.T.N.); solveig.meles@ 123456edu.univ-paris13.fr (S.M.); eurydice.angeli@ 123456gmail.com (E.A.); philipperatajczak@ 123456gmail.com (P.R.); he.lu@ 123456inserm.fr (H.L.); melanie.dibenedetto@ 123456univ-paris13.fr (M.D.B.)

[2 ]Laboratoire de Pathologie, Université Paris Diderot, Sorbonne Paris Cité, UMR_S1165, F-75010 Paris, France

[3 ]Hôpital de La Porte Verte, F-78004 Versailles, France

[4 ]Université Paris 13, F-93430 Villetaneuse, France

[5 ]Service d’Oncologie Médicale, AP-HP-Hôpital Avicenne, F-93008 Bobigny, France

[6 ]Service de Pathologie, AP-HP-Hôpital Saint-Louis, F-75010 Paris, France

Author notes

[* ]Correspondences: guilhem.bousquet@ 123456aphp.fr (G.B.); anne.janin1165@ 123456gmail.com (A.J.); Tel.: +33-142-385-428 (G.B.); +33-142-494-570 (A.J.)

[†]

These authors are co-premier authors.

[‡]

These authors are co-senior authors.

Author information

Toni Nunes https://orcid.org/0000-0001-6935-7073

Diaddin Hamdan https://orcid.org/0000-0002-2212-0287

Christophe Leboeuf https://orcid.org/0000-0002-6537-0550

He Lu https://orcid.org/0000-0003-1592-0355

Mélanie Di Benedetto https://orcid.org/0000-0003-1119-3752

Anne Janin https://orcid.org/0000-0002-9595-6261

Article

Publisher ID: ijms-19-04036

DOI: 10.3390/ijms19124036

PMC ID: 6321478

PubMed ID: 30551640

SO-VID: ea14f96b-f87a-4ef8-8451-42033b50e319

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Targeting Cancer Stem Cells to Overcome Chemoresistance

Read this article at

Abstract

Related collections

Stress signalling in stem cells

Most cited references 182

Identification of pancreatic cancer stem cells.

CD44: from adhesion molecules to signalling regulators.

Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 873

Cited by 59

Most referenced authors 4,644