Related Experiment Video
Updated: May 20, 2026
Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
Published on: June 9, 2023
Cancer Therapy Targeting the HER2-PI3K Pathway: Potential Impact on the Heart
Giannoula L Klement1, David Goukassian, Lynn Hlatky
1Center of Cancer Systems Biology, St. Elizabeth's Medical Center, Tufts University School of Medicine Boston, MA, USA.
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.
Insights
Targeting the HER2-PI3K pathway for cancer treatment can cause heart failure. Research reviews this pathway
Area of Science:
- Oncology
- Cardiology
- Molecular Biology
Background:
- The HER2-PI3K pathway is frequently mutated in cancer, with targeted therapies approved or in clinical trials.
- This pathway is crucial for normal heart function, particularly under stress.
- Cancer therapies targeting HER2 and PI3K can lead to significant cardiac dysfunction.
Purpose of the Study:
- To review the dual role of the HER2-PI3K pathway in cancer and cardiac physiology.
- To discuss the mechanisms behind therapy-induced cardiotoxicity.
- To explore strategies for mitigating cardiac side effects of pathway inhibition.
Main Methods:
- Review of clinical trial data on HER2-targeted therapies and cardiotoxicity.
- Analysis of findings from transgenic mouse models investigating pathway kinase roles in cardiac function.
- Synthesis of research on PI3K isoform-specific effects in cardiac disease.
Main Results:
- Concurrent doxorubicin and Trastuzumab treatment significantly increases heart failure risk.
- Key kinases (PI3Kα, PDK1, Akt, mTOR) protect the heart from stress-induced dysfunction.
- PI3Kγ inhibition may improve cardiac function in failing hearts, contrasting with some transgenic model outcomes.
Conclusions:
- Inhibition of the HER2-PI3K pathway presents a therapeutic dilemma due to its dual role in cancer and heart.
- Understanding isoform-specific functions is critical for developing safer cancer treatments.
- Further research is needed to balance anti-cancer efficacy with cardiovascular safety.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:38Mitogens and the Cell Cycle
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...