Hyperactivated mTOR and JAK2/STAT3 Pathways: Molecular Drivers and Potential Therapeutic Targets of Inflammatory and Invasive Ductal Breast Cancers After Neoadjuvant Chemotherapy

Clinical Breast Cancer
Komal JhaveriRobert J Schneider

Abstract

Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data showed strong activation of the phosphatidylinositide-3-kinase/mammalian target of rapamycin (mTOR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, and expression of inflammatory cytokines and tumor-associated macrophages (TAMs). Archival tumor tissue from 3 disease types (IBC treated with neoadjuvant chemotherapy [NAC], n = 45; invasive ductal carcinoma [IDC] treated with NAC [n = 24; 'treated IDC'; and untreated IDC [n = 27; 'untreated IDC']) was analyzed for the expression of biomarkers phospho-S6 (pS6) (mTOR), phospho-JAK2 (pJAK2), pSTAT3, interleukin (IL)-6, CD68 (monocytes, macrophages), and CD163 (TAMs). Surrounding nontumor tissue was also analyzed. Biomarker levels and surrogate activity according to site-specific phosphorylation were shown in the tumor tissue of all 3 disease types but were greatest in IBC and treated IDC and least in untreated IDC for pS6, pJAK2, pSTAT3, and IL-6. Of 37 IBC patients with complete biomarker data available, 100% were pS6-positive and 95% were pJAK2-positive. In nontumor tissue, biomark...Continue Reading

References

Nov 20, 2001·International Journal of Oncology·G BerclazP D Smith
Dec 31, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Harold J BursteinEric P Winer
Mar 3, 2004·The Journal of Pathology·Emmanuelle Charafe-JauffretPatrice Viens
Nov 19, 2004·Cancer Research·Michelle ThomasMarion P Boland
Dec 9, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ilse Van der AuweraLuc Y Dirix
Feb 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jenny C ChangPeter O'Connell
Mar 22, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Judith HurleyDennis J Slamon
Feb 6, 2008·BMC Cancer·Florence LereboursIvan Bieche
Apr 1, 2008·Breast Cancer Research and Treatment·Theresa CaseyKaren Plaut
Apr 29, 2008·Nature Medicine·Greg FinakMorag Park
Apr 9, 2009·Pharmacogenetics and Genomics·Soo-Chin LeeBoon-Cher Goh
May 27, 2009·Nature Reviews. Clinical Oncology·Hideko YamauchiNaoto T Ueno
Jun 16, 2009·Nature Cell Biology·Deborah SilveraRobert J Schneider
Sep 17, 2009·Cell Cycle·Deborah Silvera, Robert J Schneider
Jun 22, 2010·Cancer·François BertucciPatrice Viens
Jun 10, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hamouda BoussenNeil Spector
Dec 15, 2010·Breast Cancer Research and Treatment·Takayuki IwamotoNaoto T Ueno
Jun 3, 2011·The Journal of Clinical Investigation·Lauren L C MarottaKornelia Polyak
Dec 14, 2011·The New England Journal of Medicine·José BaselgaGabriel N Hortobagyi
May 16, 2012·The Oncologist·Hideko YamauchiNaoto T Ueno
Feb 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven J Van LaereFrançois Bertucci
Feb 15, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alfonso Quintás-Cardama, Srdan Verstovsek
Apr 10, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Luca GianniVladimir Semiglazov
Oct 12, 2013·Nature Communications·Kosuke YoshiharaRoel G W Verhaak
Oct 31, 2013·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Adrian BritschgiMohamed Bentires-Alj
Dec 3, 2013·The International Journal of Biochemistry & Cell Biology·Mona M MohamedMohamed El-Shinawi
Jul 8, 2014·The Breast : Official Journal of the European Society of Mastology·François BertucciSteven Van Laere

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Citations

Oct 25, 2016·Gynecologic Oncology·Alma Delia Campos-ParraCarlos Pérez-Plasencia
Jun 12, 2018·The British Journal of Radiology·Valentina BravatàGiorgio Russo
Apr 29, 2018·Nature Reviews. Cancer·Bora LimNaoto T Ueno
Aug 7, 2019·Breast Cancer Research : BCR·Bradley A HancockMilan Radovich
Sep 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiaojia JiWeifan Zheng
Feb 10, 2018·Expert Review of Molecular Diagnostics·Suruchi MittalIngunn Holen
Sep 5, 2020·Cancers·Xiaoping WangNaoto T Ueno
Aug 16, 2019·Molecular Cancer Therapeutics·Anna R MichmerhuizenCorey Speers
Oct 30, 2020·Breast Cancer : Targets and Therapy·Barbora Dobiasova, Michal Mego
Apr 25, 2021·Current Treatment Options in Oncology·Elena Vagia, Massimo Cristofanilli
May 1, 2021·Journal of Personalized Medicine·Valentina BravatàGiorgio Russo
Jun 3, 2021·International Journal of Molecular Sciences·Sana HibinoKoji Taniguchi
Jun 15, 2021·Breast Disease·Paul H Levine, Carmela C Veneroso
May 29, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alessio LeporeSalvatore Papa
Oct 10, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jongmin HanHyeong-Gon Moon

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