The role of phenotypic plasticity in the escape of cancer cells from targeted therapy

Biochemical Pharmacology
Michael F EmmonsKeiran S M Smalley

Abstract

Targeted therapy has proven to be beneficial at producing significant responses in patients with a wide variety of cancers. Despite initially impressive responses, most individuals ultimately fail these therapies and show signs of drug resistance. Very few patients are ever cured. Emerging evidence suggests that treatment of cancer cells with kinase inhibitors leads a minor population of cells to undergo a phenotypic switch to a more embryonic-like state. The adoption of this state, which is analogous to an epithelial-to-mesenchymal transition, is associated with drug resistance and increased tumor aggressiveness. In this commentary we will provide a comprehensive analysis of the mechanisms that underlie the embryonic reversion that occurs on targeted cancer therapy and will review potential novel therapeutic strategies designed to eradicate the escaping cells.

References

Jan 22, 2017·Experimental Dermatology·Nikolas K Haass, Brian Gabrielli
Dec 9, 2017·Cell Communication and Signaling : CCS·Nicoletta FerrariPaola Barboro
Sep 13, 2019·Expert Review of Proteomics·Marilyne LabrieGordon B Mills
Oct 3, 2019·Genes & Development·Florian RambowColin R Goding
Oct 5, 2019·Cancers·Mehwish Khaliq, Mohammad Fallahi-Sichani
Feb 22, 2020·PLoS Computational Biology·Natacha Comandante-LouMohammad Fallahi-Sichani
Jul 4, 2018·International Journal of Molecular Sciences·Matteo CapaiaPaola Barboro
Apr 8, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Tenley C ArcherScott L Pomeroy
May 5, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Viera BohacovaAlbert Breier
Dec 11, 2019·International Journal of Molecular Sciences·Roberto BenelliNicoletta Ferrari
Oct 13, 2020·Frontiers in Oncology·Jorgelindo da Veiga MoreiraMario Jolicoeur

Citations

Jan 1, 1995·Acta Anatomica·E D Hay
Sep 29, 2000·Biochemical Pharmacology·B BoyerN Edme
Apr 5, 2001·The New England Journal of Medicine·B J DrukerCharles Sawyers
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Aug 19, 2003·Nature Reviews. Molecular Cell Biology·Stefan GrünertHartmut Beug
Nov 30, 2005·Nucleic Acids Research·Cindy VandewalleGeert Berx
Dec 3, 2005·Genes & Development·Joan MassaguéDavid Wotton
Dec 22, 2006·Genes & Development·Suzanne CarreiraColin R Goding
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·James TsaiGideon Bollag
Jul 17, 2008·Pigment Cell & Melanoma Research·Satoru YokoyamaDavid E Fisher
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri, Robert A Weinberg
Jun 3, 2009·The Journal of Clinical Investigation·Hervé AcloqueM Angela Nieto
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Caroline M EmeryLevi A Garraway
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Jun 4, 2010·Biochemical Pharmacology·Takeshi YoshidaEric B Haura
Oct 29, 2010·The New England Journal of Medicine·Eunice L KwakA John Iafrate
Oct 29, 2010·The New England Journal of Medicine·Young Lim ChoiALK Lung Cancer Study Group
Nov 3, 2010·American Journal of Respiratory and Critical Care Medicine·Tzu-Hua ChangPan-Chyr Yang
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Apr 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ryohei KatayamaAlice T Shaw
Jun 4, 2011·Biochemical Pharmacology·Inna V FedorenkoKeiran S M Smalley
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanBRIM-3 Study Group
Mar 8, 2012·Melanoma Research·Vito W RebeccaKeiran S M Smalley
Jul 4, 2012·Nature Genetics·Zhenfeng ZhangTrever G Bivona
Aug 4, 2012·Cell Death and Differentiation·Y Shao, A E Aplin
Dec 1, 2012·Current Opinion in Oncology·Yoko KatsunoRik Derynck

Related Concepts

Embryo
Drug Delivery Systems
Neoplasms
Antineoplastic Chemotherapy Protocols
Epithelial to Mesenchymal Transition
Cancer Treatment
Tumor Cells, Malignant
Drug Resistance
Analysis
Malignant Neoplasms

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.