Literature DB >> 30244621

Does Axl have potential as a therapeutic target in pancreatic cancer?

Wenting Du1, Rolf A Brekken1.   

Abstract

INTRODUCTION: Pancreatic cancer is a leading cause of cancer-related death. Metastasis, therapy resistance, and immunosuppression are dominant characteristics of pancreatic tumors. Strategies that enhance the efficacy of standard of care and/or immune therapy are likely the most efficient route to improve overall survival in this disease. Areas covered: Axl, a member of the TAM (Tyro3, Axl, MerTK) family of receptor tyrosine kinases, is involved in cell plasticity, chemoresistance, immune suppression, and metastasis in various cancers, including pancreatic cancer. This review provides an overview of Axl and its function in normal conditions, summarizes the regulation and function of Axl in cancer, and highlights the contribution of Axl to pancreatic cancer as well as its potential as a therapeutic target. Expert opinion: Axl is an attractive therapeutic target in pancreatic cancer because it contributes to many of the roadblocks that hamper therapeutic efficacy. Clinical evidence supporting Axl inhibition in pancreatic cancer is currently limited; however, multiple clinical trials have been initiated or are in the planning phase to test the effect of inhibiting Axl in conjunction with standard therapy in pancreatic cancer patients. We anticipate that these studies will provide robust validation of Axl as a therapeutic target in pancreatic cancer.

Entities:  

Keywords:  Axl; epithelial plasticity; immunosuppression; metastasis; pancreatic cancer; therapy resistance

Mesh:

Substances:

Year:  2018        PMID: 30244621      PMCID: PMC6292430          DOI: 10.1080/14728222.2018.1527315

Source DB:  PubMed          Journal:  Expert Opin Ther Targets        ISSN: 1472-8222            Impact factor:   6.902


  124 in total

1.  Gas6/Axl pathway is activated in chronic liver disease and its targeting reduces fibrosis via hepatic stellate cell inactivation.

Authors:  Cristina Bárcena; Milica Stefanovic; Anna Tutusaus; Leonel Joannas; Anghara Menéndez; Carmen García-Ruiz; Pau Sancho-Bru; Montserrat Marí; Joan Caballeria; Carla V Rothlin; José C Fernández-Checa; Pablo García de Frutos; Albert Morales
Journal:  J Hepatol       Date:  2015-04-20       Impact factor: 25.083

2.  Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances Chemotherapy in Pancreatic Cancer.

Authors:  Kathleen F Ludwig; Wenting Du; Noah B Sorrelle; Katarzyna Wnuk-Lipinska; Mary Topalovski; Jason E Toombs; Victoria H Cruz; Shinichi Yabuuchi; N V Rajeshkumar; Anirban Maitra; James B Lorens; Rolf A Brekken
Journal:  Cancer Res       Date:  2017-11-27       Impact factor: 12.701

3.  Receptor tyrosine kinase Axl is required for resistance of leukemic cells to FLT3-targeted therapy in acute myeloid leukemia.

Authors:  I-K Park; B Mundy-Bosse; S P Whitman; X Zhang; S L Warner; D J Bearss; W Blum; G Marcucci; M A Caligiuri
Journal:  Leukemia       Date:  2015-06-19       Impact factor: 11.528

Review 4.  Axl kinase as a key target for oncology: focus on small molecule inhibitors.

Authors:  Clémence Feneyrolles; Aurélia Spenlinhauer; Léa Guiet; Bénédicte Fauvel; Bénédicte Daydé-Cazals; Pierre Warnault; Gwénaël Chevé; Aziz Yasri
Journal:  Mol Cancer Ther       Date:  2014-08-19       Impact factor: 6.261

5.  Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through Axl gene expression in solid cancer.

Authors:  Giridhar Mudduluru; Peter Vajkoczy; Heike Allgayer
Journal:  Mol Cancer Res       Date:  2010-02-09       Impact factor: 5.852

6.  Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

Authors:  Marguerite L Palisoul; Jeanne M Quinn; Emily Schepers; Ian S Hagemann; Lei Guo; Kelsey Reger; Andrea R Hagemann; Carolyn K McCourt; Premal H Thaker; Matthew A Powell; David G Mutch; Katherine C Fuh
Journal:  Mol Cancer Ther       Date:  2017-09-13       Impact factor: 6.261

7.  Axl/Gas6 pathway positively regulates FLT3 activation in human natural killer cell development.

Authors:  Il-Kyoo Park; Rossana Trotta; Jianhua Yu; Michael A Caligiuri
Journal:  Eur J Immunol       Date:  2013-07-08       Impact factor: 5.532

8.  Dicer Elicits Paclitaxel Chemosensitization and Suppresses Cancer Stemness in Breast Cancer by Repressing AXL.

Authors:  Ting-Yu Chang; Hsin-An Chen; Ching-Feng Chiu; Yi-Wen Chang; Tsang-Chih Kuo; Po-Chun Tseng; Weu Wang; Mien-Chie Hung; Jen-Liang Su
Journal:  Cancer Res       Date:  2016-05-23       Impact factor: 12.701

9.  Targeting Axl with an high-affinity inhibitory aptamer.

Authors:  Laura Cerchia; Carla L Esposito; Simona Camorani; Anna Rienzo; Loredana Stasio; Luigi Insabato; Andrea Affuso; Vittorio de Franciscis
Journal:  Mol Ther       Date:  2012-08-21       Impact factor: 11.454

10.  Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy.

Authors:  Derek B Oien; Tamás Garay; Sarah Eckstein; Jeremy Chien
Journal:  Front Pharmacol       Date:  2018-01-11       Impact factor: 5.810

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  9 in total

Review 1.  The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.

Authors:  Andres Garcia-Sampedro; Gabriella Gaggia; Alexander Ney; Ismahan Mahamed; Pilar Acedo
Journal:  J Clin Med       Date:  2021-02-03       Impact factor: 4.241

2.  AXL Inhibitor TP-0903 Reduces Metastasis and Therapy Resistance in Pancreatic Cancer.

Authors:  Yuqing Zhang; Emily N Arner; Ali Rizvi; Jason E Toombs; Huocong Huang; Steven L Warner; Jason M Foulks; Rolf A Brekken
Journal:  Mol Cancer Ther       Date:  2021-10-21       Impact factor: 6.009

3.  Sitravatinib potentiates immune checkpoint blockade in refractory cancer models.

Authors:  Wenting Du; Huocong Huang; Noah Sorrelle; Rolf A Brekken
Journal:  JCI Insight       Date:  2018-11-02

Review 4.  Targeting TAM to Tame Pancreatic Cancer.

Authors:  Mitchell S von Itzstein; Michael C Burke; Rolf A Brekken; Todd A Aguilera; Herbert J Zeh; Muhammad Shaalan Beg
Journal:  Target Oncol       Date:  2020-10       Impact factor: 4.493

5.  AXL Is a Key Factor for Cell Plasticity and Promotes Metastasis in Pancreatic Cancer.

Authors:  Wenting Du; Natalie Z Phinney; Huocong Huang; Zhaoning Wang; Jill Westcott; Jason E Toombs; Yuqing Zhang; Muhammad S Beg; Thomas M Wilkie; James B Lorens; Rolf A Brekken
Journal:  Mol Cancer Res       Date:  2021-04-02       Impact factor: 5.852

Review 6.  Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers.

Authors:  Emily N Arner; Wenting Du; Rolf A Brekken
Journal:  Front Oncol       Date:  2019-10-11       Impact factor: 6.244

7.  Radioactive 125I seed implantation for pancreatic cancer with unexpected liver metastasis: A preliminary experience with 26 patients.

Authors:  Cheng-Gang Li; Zhi-Peng Zhou; Yu-Ze Jia; Xiang-Long Tan; Yu-Yao Song
Journal:  World J Clin Cases       Date:  2021-02-06       Impact factor: 1.337

8.  Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis.

Authors:  Gaia Bellomo; Carolyn Rainer; Valeria Quaranta; Yuliana Astuti; Meirion Raymant; Elzbieta Boyd; Ruth Stafferton; Fiona Campbell; Paula Ghaneh; Christopher M Halloran; Dean E Hammond; Jennifer P Morton; Daniel Palmer; Dale Vimalachandran; Robert Jones; Ainhoa Mielgo; Michael C Schmid
Journal:  Gut       Date:  2022-01-12       Impact factor: 31.793

Review 9.  TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy.

Authors:  Adam S Dayoub; Rolf A Brekken
Journal:  Cell Commun Signal       Date:  2020-02-22       Impact factor: 5.712

  9 in total

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