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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
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Comprehensive Analysis Identifies Variability in PI3K Pathway Alterations in Triple-Negative Breast Cancer Subtypes.
Reva K Basho1, Li Zhao2, Jason B White2
1Ellison Institute of Technology, Los Angeles, CA.
JCO Precision Oncology
|March 14, 2024
Summary
Alterations in the PI3K pathway are common in triple-negative breast cancer (TNBC) and impact treatment response. These genetic changes, particularly in M and LAR subtypes, may guide targeted therapy development for improved outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) exhibits frequent alterations in the PI3K pathway.
- Mesenchymal (M) and Luminal Androgen Receptor (LAR) TNBC subtypes show a higher incidence of PI3K pathway alterations.
- The specific impact of these alterations across diverse TNBC subtypes remains unclear.
Purpose of the Study:
- To investigate the incidence of PI3K pathway alterations across distinct TNBC subtypes.
- To correlate PI3K pathway alterations with pathologic response to neoadjuvant therapy (NAT) in TNBC patients.
- To understand the clinical significance of PI3K pathway alterations in TNBC subtypes.
Main Methods:
- Evaluated pretreatment tumor samples from 177 operable TNBC patients on a NAT clinical trial.
- Classified tumors into seven TNBC subtypes using Pietenpol criteria.
- Analyzed 32 PI3K pathway-activating genes for alterations (mutations, PTEN loss) via whole-exome sequencing, RNA sequencing, and immunohistochemistry.
Main Results:
- Significant differences in PI3K pathway alteration incidence were observed across TNBC subtypes (P < .01).
- LAR (81%), BL2 (79%), and M (62%) subtypes had the highest alteration rates.
- PIK3CA mutation correlated with pathologic complete response (pCR) in the LAR subtype (P = .02).
Conclusions:
- PI3K pathway alterations influence neoadjuvant therapy response in TNBC.
- Targeted therapies hold promise for improving outcomes, especially in M and LAR TNBC patients.
- Further research into PI3K pathway-targeted agents is warranted for specific TNBC subtypes.
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