Ariella Hanker, Ph.D.

Dr. Hanker received her B.Sc. in chemistry from the University of Virginia in 2004 and Ph.D. in genetics and molecular biology from the University of North Carolina at Chapel Hill in 2009. Her graduate work in the laboratory of Dr. Channing Der focused on strategies to disrupt membrane binding of the small GTPase Rheb, in an effort to block aberrant Rheb/mTOR signaling in cancer. Dr. Hanker pursued postdoctoral training in the laboratory of Dr. Carlos Arteaga at Vanderbilt University Medical Center. During this time, she was awarded a postdoctoral fellowship from the Department of Defense Breast Cancer Research Program and a career development award (K12 award) from the National Cancer Institute. Her postdoctoral studies used transgenic mouse models and human breast cancer xenografts to study mechanisms of resistance to HER2-targeted therapy in HER2+ breast cancer. More recently, Dr. Hanker identified the HER2 T798I gatekeeper mutation as a mechanism of resistance to HER2-targeted therapy in HER2-mutant breast cancer.

Dr. Hanker's current work is focused on 1) therapeutic targeting of breast cancer-associated alterations, and 2) delineating mechanisms of resistance to breast cancer targeted therapies, including HER2 inhibitors, antiestrogens, PI3K/AKT inhibitors, and CDK4/6 inhibitors.

Dr. Hanker joined the faculty of UT Southwestern Medical Center in 2018. Her research program is supported by grants from the National Cancer Institute and the Breast Cancer Research Foundation.

Undergraduate

University of Virginia - Sfs (2004), Chemistry

Graduate School

University of N C-Chapel Hill (2009)

• breast cancer targeted therapy
• cancer biology
• cancer genomics
• drug resistance
• PI3K pathway
• precision oncology
• receptor tyrosine kinases
• signal transduction

Featured Publications

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

Jhaveri K, Eli LD, Wildiers H, Hurvitz SA, Guerrero-Zotano A, Unni N, Brufsky A, Park H, Waisman J, Yang ES, Spanggaard I, Reid S, Burkard ME, Vinayak S, Prat A, Arnedos M, Bidard FC, Loi S, Crown J, Bhave M, Piha-Paul SA, Suga JM, Chia S, Saura C, Garcia-Saenz JÁ, Gambardella V, de Miguel MJ, Gal-Yam EN, Rapael A, Stemmer SM, Ma C, Hanker AB, Ye D, Goldman JW, Bose R, Peterson L, Bell JSK, Frazier A, DiPrimeo D, Wong A, Arteaga CL, Solit DB, Ann Oncol 2023 Oct 34 10 885-898

Acquired secondary HER2 mutations enhance HER2/MAPK signaling and promote resistance to HER2 kinase inhibition in breast cancer.

Marin A, Mamun AA, Patel H, Akamatsu H, Ye D, Sudhan DR, Eli L, Marcelain K, Brown BP, Meiler J, Arteaga CL, Hanker AB, Cancer Res 2023 Jul

Co-occurring gain-of-function mutations in HER2 and HER3 modulate HER2/HER3 activation, oncogenesis, and HER2 inhibitor sensitivity.

Hanker AB, Brown BP, Meiler J, Marín A, Jayanthan HS, Ye D, Lin CC, Akamatsu H, Lee KM, Chatterjee S, Sudhan DR, Servetto A, Brewer MR, Koch JP, Sheehan JH, He J, Lalani AS, Arteaga CL, Cancer Cell 2021 Jun

Proline rich 11 (PRR11) overexpression amplifies PI3K signaling and promotes antiestrogen resistance in breast cancer.

Lee KM, Guerrero-Zotano AL, Servetto A, Sudhan DR, Lin CC, Formisano L, Jansen VM, González-Ericsson P, Sanders ME, Stricker TP, Raj G, Dean KM, Fiolka R, Cantley LC, Hanker AB, Arteaga CL, Nat Commun 2020 10 11 1 5488

Overcoming Endocrine Resistance in Breast Cancer.

Hanker AB, Sudhan DR, Arteaga CL, Cancer Cell 2020 Apr 37 4 496-513

Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers.

Sudhan DR, Guerrero-Zotano A, Won H, González Ericsson P, Servetto A, Huerta-Rosario M, Ye D, Lee KM, Formisano L, Guo Y, Liu Q, Kinch LN, Red Brewer M, Dugger T, Koch J, Wick MJ, Cutler RE, Lalani AS, Bryce R, Auerbach A, Hanker AB, Arteaga CL, Cancer Cell 2020 Jan

Challenges for the Clinical Development of PI3K Inhibitors: Strategies to Improve Their Impact in Solid Tumors.

Hanker AB, Kaklamani V, Arteaga CL Cancer Discov 2019 Mar

An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.

Hanker AB, Brewer MR, Sheehan JH, Koch JP, Sliwoski GR, Nagy R, Lanman R, Berger MF, Hyman DM, Solit DB, He J, Miller V, Cutler RE, Lalani AS, Cross D, Lovly CM, Meiler J, Arteaga CL Cancer Discov 2017 06 7 6 575-585

AXL/WRNIP1 mediates replication stress response and promotes therapy resistance and metachronous metastasis in HER2+ breast cancer.

Marquez-Palencia M, Reza Herrera L, Parida PK, Ghosh S, Kim K, Das NM, Gonzalez-Ericsson PI, Sanders ME, Mobley BC, Diegeler S, Aguilera TA, Peng Y, Lewis CM, Arteaga CL, Hanker AB, Whitehurst AW, Lorens JB, Brekken RA, Davis AJ, Malladi S, Cancer Res 2024 Jan

ZNF397 Loss Triggers TET2-driven Epigenetic Rewiring, Lineage Plasticity, and AR-targeted Therapy Resistance in AR-dependent Cancers.

Xu Y, Wang Z, Sjöström M, Deng S, Wang C, Johnson NA, Gonzalez J, Li X, Metang LA, Tirado CR, Mukherji A, Wainwright G, Yu X, Yang Y, Barnes S, Hofstad M, Zhu H, Hanker A, He HH, Chen Y, Wang Z, Raj G, Arteaga C, Feng F, Wang Y, Wang T, Mu P, bioRxiv 2023 Oct

 Featured Books

The Roles of Ras Family Small GTPases in Breast Cancer. In Handbook of Cell Signaling 2ed

Hanker AB, Der CJ (2009). Cambridge, MA, Academic Press

Role of R-Ras in Cell Growth. In Handbook of Cell Signaling 2ed

Repasky GA, Cox AD, Hanker AB, Mitin N, Der CJ (2009). Cambridge, MA, Academic Press

• AACR NextGen Star
  (2022)
• Breast Cancer Research Foundation Award - Abemaciclib Research Program
  (2020-2023)
• NIH/NCI SPORE in Breast Cancer Career Enhancement Award
  (2016)
• AACR-Susan G. Komen Scholar-in-Training Award, San Antonio Breast Cancer Symposium
  (2014)
• Vanderbilt Clinical Oncology Research Career Development Award (K12)
  (2014)
• AACR-Aflac, Inc. Scholar-in-Training Award
  (2013)
• Department of Defense Breast Cancer Research Program Postdoctoral Fellowship Award
  (2011)
• Department of Defense Breast Cancer Research Program Predoctoral Traineeship Award
  (2006)
• Highest Distinction, University of Virginia Distinguished Majors Project
  (2004)

• American Association for Cancer Research (2009)
• Cancer Biology graduate program (2022)
• Cell and Molecular Biology graduate program (2022)
• Experimental Therapeutics Program, Harold C. Simmons Comprehensive Cancer Center (2019)
• Ipatasertib Project Team, National Cancer Institute Cancer Therapy Evaluation Program (NCI CTEP) (2020-2020)