ArticleFrontiers in pharmacology2012
Cancer Therapy Targeting the HER2-PI3K Pathway: Potential Impact on the Heart.
Article in Frontiers in pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Signaling pathways and potential therapeutic agents in trastuzumab-induced cardiotoxicity.Apoptosis : an international journal on programmed cell death · 2026Review
- Multifaceted roles of melatonin in oncology: an insight into its therapeutic potential in cancer management.Inflammopharmacology · 2025Review
- Potential bidirectional regulatory effects of botanical drug metabolites on tumors and cardiovascular diseases based on the PI3K/Akt/mTOR pathway.Frontiers in pharmacology · 2025Review
- Melatonin as a regulator of apoptosis in leukaemia: molecular mechanism and therapeutic perspectives.Frontiers in pharmacology · 2023Review
- Development of an adverse outcome pathway network for breast cancer: a comprehensive representation of the pathogenesis, complexity and diversity of the disease.Archives of toxicology · 2022Review
- HER2 c-Terminal Fragments Are Expressed via Internal Translation of the HER2 mRNA.International journal of molecular sciences · 2022Article
- Trastuzumab aggravates radiation induced cardiotoxicity in mice.American journal of cancer research · 2022Article
- Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model.PloS one · 2018Article
- Perspective on the dynamics of cancer.Theoretical biology & medical modelling · 2017Review
- Hyperthermia induced HIF-1a expression of lung cancer through AKT and ERK signaling pathways.Journal of experimental & clinical cancer research : CR · 2016Article
- Doxorubicin resistance in breast cancer is driven by light at night-induced disruption of the circadian melatonin signal.Journal of pineal research · 2015Article
- A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications.Biochimica et biophysica acta · 2013Review
- 3-Phosphoinositide-dependent protein kinase-1 as an emerging target in the management of breast cancer.Cancer management and research · 2013Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The HER2-PI3K pathway is the one of the most mutated pathways in cancer. Several drugs targeting the major kinases of this pathway have been approved by the Food and Drug Administration and many are being tested in clinical trials for the treatment of various cancers. However, the HER2-PI3K pathway is also pivotal for maintaining the physiological function of the heart, especially in the presence of cardiac stress. Clinical studies have shown that in patients treated with doxorubicin concurrently with Trastuzumab, a monoclonal antibody that blocks the HER2 receptor, the New York Heart Association class III/IV heart failure was significantly increased compared to those who were treated with doxorubicin alone (16 vs. 3%). Studies in transgenic mice have also shown that other key kinases of this pathway, such as PI3Kα, PDK1, Akt, and mTOR, are important for protecting the heart from ischemia-reperfusion and aortic stenosis induced cardiac dysfunction. Studies, however, have also shown that inhibition of PI3Kγ improve cardiac function of a failing heart. In addition, results from transgenic mouse models are not always consistent with the outcome of the pharmacological inhibition of this pathway. Here, we will review these findings and discuss how we can address the cardiac side-effects caused by inhibition of this important pathway in both cancer and cardiac biology.
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