Related Experiment Video
Updated: Jul 3, 2025
Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer
Amy H Tien1, Marianne D Sadar1,2
1Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
Abstract:
Breast cancer is a major cause of death worldwide. The complexity of endocrine regulation in breast cancer may allow the cancer cells to escape from a particular treatment and result in resistant and aggressive disease. These breast cancers usually have fewer treatment options. Targeted therapies for cancer patients may offer fewer adverse side effects because of specificity compared to conventional chemotherapy. Signaling pathways of nuclear receptors, such as the estrogen receptor (ER), have been intensively studied and used as therapeutic targets. Recently, the role of the androgen receptor (AR) in breast cancer is gaining greater attention as a therapeutic target and as a prognostic biomarker. The expression of constitutively active truncated AR splice variants in breast cancer is a possible mechanism contributing to treatment resistance. Therefore, targeting both the full-length AR and AR variants, either through the activation or suppression of AR function, depending on the status of the ER, progesterone receptor, or human epidermal growth factor receptor 2, may provide additional treatment options. Studies targeting AR in combination with other treatment strategies are ongoing in clinical trials. The determination of the status of nuclear receptors to classify and identify patient subgroups will facilitate optimized and targeted combination therapies.
Insights
Androgen receptor (AR) targeting offers new breast cancer treatment options, especially for resistant cases. Understanding AR status and targeting it with other therapies may improve patient outcomes.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Breast cancer is a leading cause of global mortality.
- Endocrine resistance in breast cancer limits treatment options and increases disease aggressiveness.
- Targeted therapies, including those modulating nuclear receptors, show promise over conventional chemotherapy.
Purpose of the Study:
- To highlight the emerging role of the androgen receptor (AR) as a therapeutic target and prognostic biomarker in breast cancer.
- To explore the significance of AR splice variants in treatment resistance.
- To discuss the potential of targeting AR, in conjunction with other receptors, for improved breast cancer management.
Main Methods:
- Review of current literature on nuclear receptor signaling in breast cancer.
- Analysis of the role of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 in conjunction with AR.
- Examination of ongoing clinical trials investigating AR-targeted therapies.
Main Results:
- The androgen receptor (AR) is increasingly recognized as a critical factor in breast cancer, particularly in endocrine-resistant forms.
- Constitutively active truncated AR splice variants are implicated in treatment resistance.
- Targeting AR, alongside ER, progesterone receptor, or HER2 status, presents a promising strategy for novel therapeutic combinations.
Conclusions:
- Modulating androgen receptor (AR) function, by activation or suppression, offers potential new avenues for treating breast cancer, especially resistant subtypes.
- Determining nuclear receptor status is crucial for stratifying patients and optimizing combination therapies.
- Further clinical trials are essential to validate AR-targeted strategies in breast cancer treatment.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
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...
02:38Mitogens and the Cell Cycle
02:56Treatment Resistant Cancers
01:32RNA Splicing
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...