A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer.
Katrien Berns,Hugo M. Horlings,Bryan T. Hennessy,Mandy Madiredjo,E. Marielle Hijmans,Karin Beelen,Sabine C. Linn,Ana M. Gonzalez-Angulo,Katherine Stemke-Hale,Michael Hauptmann,Roderick L. Beijersbergen,Gordon B. Mills,Marc J. van de Vijver,René Bernards +13 more
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TL;DR: Assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone.
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About: This article is published in Cancer Cell. The article was published on 16 Oct 2007. and is currently open access. The article focuses on the topics: Trastuzumab & Breast cancer.
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Citations
Status of PI3K inhibition and biomarker development in cancer therapeutics
TL;DR: The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival, and an array of genetic mutations and amplifications has been described affecting key components of this pathway.
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Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/ PTEN mutation
Yan Xing,Nan Lin,Matthew A. Maurer,Matthew A. Maurer,Huiqin Chen,Armeen Mahvash,Aysegul A. Sahin,Argun Akcakanat,Yisheng Li,Vandana G. Abramson,Jennifer K. Litton,Mariana Chavez-MacGregor,Vicente Valero,Sarina Anne Piha-Paul,David S. Hong,Kim Anh Do,Emily Tarco,Dianna Riall,Agda Karina Eterovic,Gerburg M. Wulf,Lewis C. Cantley,Gordon B. Mills,L. Austin Doyle,Eric P. Winer,Gabriel N. Hortobagyi,Ana M. Gonzalez-Angulo,Funda Meric-Bernstam +26 more
TL;DR: MK-2206 monotherapy had limited clinical activity in advanced breast cancer patients selected for PIK3CA/AKT1 or PTEN mutations orPTEN loss, and may be due to inadequate target inhibition at tolerable doses in heavily pre-treated patients with pathway activation.
Resistance mechanisms to anti-HER2 therapies in HER2-positive breast cancer: Current knowledge, new research directions and therapeutic perspectives
Claudio Vernieri,Monica Milano,Marta Brambilla,Alessia Mennitto,Claudia Maggi,Maria Silvia Cona,Michele Prisciandaro,Chiara Fabbroni,Luigi Celio,Gabriella Mariani,Giulia Bianchi,Giuseppe Capri,Filippo de Braud +12 more
TL;DR: Defining the best strategies to delay or revert resistance to anti-HER2 treatments will be crucial to improve their clinical efficacy, and only a few mechanisms have been validated in clinical series.
189
Evaluation of the association of PIK3CA mutations and PTEN loss with efficacy of trastuzumab therapy in metastatic breast cancer.
E. Razis,Mattheos Bobos,Vassiliki Kotoula,Anastasia G Eleftheraki,Haralabos P. Kalofonos,Kitty Pavlakis,Pavlos Papakostas,Gerassimos Aravantinos,George Rigakos,Ioannis Efstratiou,Kalliopi Petraki,Dimitris Bafaloukos,Ioannis Kostopoulos,Dimitrios Pectasides,Konstantine T. Kalogeras,D.V. Skarlos,George Fountzilas +16 more
TL;DR: In this trastuzumab-treated breast cancer population, PIK3CA activating mutations were associated with shorter TTP and PTEN loss with decreased survival, indicating the adverse effect of this pathway’s status on trastizumab efficacy.
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Circulating tumour cells and cell-free DNA as tools for managing breast cancer.
Leticia De Mattos-Arruda,Javier Cortes,Libero Santarpia,Ana Vivancos,Josep Tabernero,Jorge S. Reis-Filho,Joan Seoane +6 more
TL;DR: The current status of blood-born biomarkers as surrogates for tissue-based biomarkers, and their burgeoning impact on the management of patients with breast cancer are discussed.
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TL;DR: Variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals were characterized using complementary DNA microarrays representing 8,102 human genes, providing a distinctive molecular portrait of each tumour.
Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2
Dennis J. Slamon,Brian Leyland-Jones,Steven Shak,Hank Fuchs,Virginia E. Paton,Alex Bajamonde,Thomas Fleming,Wolfgang Eiermann,Janet M. Wolter,Mark D. Pegram,José Baselga,Larry Norton +11 more
TL;DR: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a higher rate of objective response, a longer duration of response, and a lower rate of death at 1 year.
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