Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma

Cancer Cell
Hayley J SharpeFrederic J de Sauvage

Abstract

Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

References

Mar 5, 1985·Journal of Molecular Biology·J H Miller
Jun 18, 2002·Nature Genetics·Michael D TaylorDavid Hogg
Jan 20, 2005·The British Journal of Dermatology·J ReifenbergerG Reifenberger
Apr 25, 2007·Oncogene·Y LeeP J McKinnon
Jun 18, 2009·American Journal of Medical Genetics. Part a·L PastorinoG Bianchi Scarrà
Feb 24, 2010·Nature Reviews. Molecular Cell Biology·Simona NegriniThanos D Halazonetis
Oct 1, 2010·Science Translational Medicine·Silvia BuonamiciMarion Dorsch
Feb 9, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia M LoRussoDaniel D Von Hoff
Apr 5, 2011·American Journal of Human Genetics·Abel González-Pérez, Nuria López-Bigas
May 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Harvey WongStephen E Gould
Jun 23, 2011·Cancer Informatics·Susann StjernqvistChris D Greenman
May 23, 2012·Cell·Serena Nik-ZainalUNKNOWN Breast Cancer Working Group of the International Cancer Genome Consortium
Jun 8, 2012·The New England Journal of Medicine·Aleksandar SekulicAxel Hauschild
Aug 17, 2012·Future Oncology·Mark R LacknerJeff Settleman
Aug 23, 2012·Archives of Dermatology·Anne Lynn S Chang, Anthony E Oro
Oct 18, 2012·Journal of Cutaneous Pathology·Karolina A PeszMaria M Sąsiadek
Nov 13, 2012·Annual Review of Pharmacology and Toxicology·Vsevolod KatritchRaymond C Stevens
Jan 22, 2013·Nature Genetics·Priscilla K BrastianosRameen Beroukhim
Jun 19, 2013·The Journal of Investigative Dermatology·Shyam S JayaramanMichael S Kolodney
Jul 9, 2013·Nature Chemical Biology·Daniel NedelcuAdrian Salic
Oct 8, 2013·Cancer Research·Meghna Das Thakur, Darrin D Stuart
Oct 25, 2013·Cancer Research·Ciara MetcalfeFrederic J de Sauvage
Nov 10, 2013·Nature Medicine·Dereck AmakyeMarion Dorsch
Mar 22, 2014·Cancer Cell·Marcel KoolUNKNOWN ICGC PedBrain Tumor Project
May 27, 2014·Nature Genetics·Robert T SweeneyRobert B West
Oct 13, 2014·Molecular Oncology·Sabrina PriclFederica Perrone
Nov 19, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Miriam J SmithD Gareth R Evans

❮ Previous
Next ❯

Citations

Dec 5, 2015·Acta Oncologica·Gunnar JohanssonBeatrice Melin
Dec 17, 2015·Expert Opinion on Therapeutic Patents·Fabrizio Manetti, Elena Petricci
Oct 4, 2015·Trends in Pharmacological Sciences·Angela M ArensdorfStacey K Ogden
Mar 12, 2015·Cancer Cell·Todd W Ridky, George Cotsarelis
Jun 7, 2015·European Journal of Pharmacology·Yuji ShimizuMasaharu Nakayama
Mar 26, 2016·Journal of Medicinal Chemistry·Jennifer R PaceM Kyle Hadden
Aug 5, 2015·Current Problems in Cancer·Carlos Prieto-Granada, Paul Rodriguez-Waitkus
Jun 17, 2015·Biochimica Et Biophysica Acta·Laura Di MagnoGianluca Canettieri
Jun 15, 2015·Trends in Pharmacological Sciences·Paola InfanteLucia Di Marcotullio
Jul 21, 2016·Nature·Eamon F X ByrneChristian Siebold
Jul 28, 2016·Expert Opinion on Investigational Drugs·Gregory N Gan, Antonio Jimeno
Aug 25, 2016·Developmental Cell·Ekaterina Pak, Rosalind A Segal
Aug 19, 2016·Expert Opinion on Pharmacotherapy·Egle RamelyteReinhard Dummer
Sep 17, 2016·Expert Review of Anticancer Therapy·Nicholas J CollierJohn T Lear
Oct 19, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jun YangWenfu Tan
Nov 9, 2016·Biochimica Et Biophysica Acta. General Subjects·Radha Charan DashM Kyle Hadden
Apr 8, 2017·American Journal of Medical Genetics. Part a·Kristen WigbyMarilyn C Jones
Sep 2, 2016·Therapeutic Advances in Medical Oncology·Sirunya SilapuntMichael R Migden
Oct 30, 2015·Cancers·Sherri Y Huang, Jer-Yen Yang
Nov 23, 2017·International Journal of Molecular Sciences·Cristina PellegriniMaria Concetta Fargnoli
Sep 10, 2017·American Journal of Clinical Dermatology·Rebecca DanhofMariah Brown
Mar 21, 2018·American Journal of Therapeutics·Bilal KhalidMohammad Razaq
Apr 27, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Miroslava DidiasovaMalgorzata Wygrecka
Jul 26, 2018·The New England Journal of Medicine·Kishwer S Nehal, Christopher K Bichakjian
Jun 3, 2017·Molecular Carcinogenesis·Anshika BakshiMohammad Athar
Sep 18, 2018·The British Journal of Dermatology·V Haug, B Schilling
May 18, 2018·Acta Oncologica·Marla Karine AmaranteMaria Angelica Ehara Watanabe
Aug 15, 2018·Anti-cancer Drugs·Peng LinXinliang Mao
Sep 17, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M NikanjamR Kurzrock
Jan 18, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Andrea CalcaterraFrancesca Ghirga
Jul 26, 2018·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Leon ChenMichael R Migden
Jan 24, 2019·Dermatology and Therapy·Marie-Therese LecciaNicole Basset-Seguin

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Carcinoma, Basal Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.