Targeting nodal in conjunction with dacarbazine induces synergistic anticancer effects in metastatic melanoma

Molecular Cancer Research : MCR
Katharine M HardyMary J C Hendrix

Abstract

Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. Despite a complete response in fewer than 5% of patients, the chemotherapeutic agent dacarbazine (DTIC) remains the reference drug after almost 40 years. More recently, FDA-approved drugs have shown promise but patient outcome remains modest, predominantly due to drug resistance. As such, combinatorial targeting has received increased attention, and will advance with the identification of new molecular targets. One attractive target for improving melanoma therapy is the growth factor Nodal, whose normal expression is largely restricted to embryonic development, but is reactivated in metastatic melanoma. In this study, we sought to determine how Nodal-positive human melanoma cells respond to DTIC treatment and to ascertain whether targeting Nodal in combination with DTIC would be more effective than monotherapy. A single treatment with DTIC inhibited cell growth but did not induce apoptosis. Rather than reducing Nodal expression, DTIC increased the size of the Nodal-positive subpopulation, an observation coincident with increased cellular invasion. Importantly, clinical tissue specimens from patients with melanomas refractory to DTIC therapy stained po...Continue Reading

References

Jan 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J M KirkwoodR H Blum
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M B AtkinsS A Rosenberg
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Aug 4, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Alexander M M Eggermont, John M Kirkwood
Oct 27, 2004·Developmental Biology·Ludovic VallierRoger A Pedersen
Aug 8, 2006·Nature Medicine·Jolanta M TopczewskaMary J C Hendrix
Jan 4, 2007·Cancer·Helen J GogasVernon K Sondak
Feb 9, 2007·Development·Michael M Shen
May 18, 2007·The Journal of Investigative Dermatology·Christiane ThallingerChristian Joukhadar
Dec 7, 2007·International Journal of Radiation Biology·Juergen FriedrichLeoni A Kunz-Schughart
Jan 19, 2008·Nature·Tobias SchattonMarkus H Frank
Mar 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lynne-Marie PostovitMary J C Hendrix
Sep 10, 2009·Cell·Mark ShackletonSean J Morrison
Sep 29, 2009·Critical Reviews in Oncology/hematology·Roger MouawadDavid Khayat
Oct 31, 2009·Reproductive Biology and Endocrinology : RB&E·Irene PapageorgiouCraig A Harrison
Nov 4, 2009·Expert Review of Dermatology·Luigi StrizziMary Jc Hendrix
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Alexander F Schier
May 28, 2010·Journal of Cutaneous Pathology·Josephine C McAllisterGeorge F Murphy
May 25, 2010·Epigenomics·Fabricio F CostaMary J C Hendrix
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Aug 25, 2011·Development·Marianna Kruithof-de JulioMichael M Shen
Apr 4, 2012·The Lancet Oncology·Nicholas C Turner, Jorge S Reis-Filho
May 15, 2012·Breast Cancer Research : BCR·Luigi StrizziMary J C Hendrix
Jun 6, 2012·The New England Journal of Medicine·Keith T FlahertyUNKNOWN METRIC Study Group
Jun 8, 2012·PloS One·Marine ChartrainJean Philippe Annereau
Aug 18, 2012·The Journal of Pathology·Philipp Grosse-GehlingLeoni A Kunz-Schughart
Oct 2, 2012·The New England Journal of Medicine·Keith T FlahertyJeffrey Weber
Jan 8, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ryan J Sullivan, Keith T Flaherty
Jan 8, 2013·The International Journal of Biochemistry & Cell Biology·Daniela F QuailLynne-Marie Postovit
Feb 19, 2013·Oncogene·L N Kwong, M A Davies
Sep 21, 2013·Nature·Corbin E Meacham, Sean J Morrison
Oct 4, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ryan J SullivanKeith T Flaherty
Nov 12, 2013·Trends in Pharmacological Sciences·Lucio TentoriGrazia Graziani
Jul 30, 2014·Seminars in Cancer Biology·Gina KirsammerMary J C Hendrix
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertDirk Schadendorf

❮ Previous
Next ❯

Citations

Sep 16, 2015·International Journal of Molecular Sciences·Annalia FocàAnnamaria Sandomenico
Jan 26, 2016·Pharmacology & Therapeutics·Mary J C HendrixYi-Wen Chu
Mar 10, 2016·Cancer Metastasis Reviews·Thomas M BodenstineMary J C Hendrix
Mar 25, 2016·International Journal of Molecular Sciences·Naira V MargaryanLuigi Strizzi
Oct 25, 2016·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mary Jc HendrixRichard A Scolyer
Sep 13, 2018·Current Medicinal Chemistry·Annamaria Sandomenico, Menotti Ruvo
Oct 16, 2015·Oncotarget·Luigi StrizziMary J C Hendrix
Feb 19, 2020·Anti-cancer Agents in Medicinal Chemistry·Yeliz DemirŞükrü Beydemir
Nov 21, 2017·Current Molecular Biology Reports·Naira V MargaryanMary J C Hendrix
Mar 13, 2019·Cancers·Naira V MargaryanMary J C Hendrix
Aug 13, 2021·Frontiers in Oncology·Giuliana CataraDaniela Spano

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

© 2021 Meta ULC. All rights reserved