A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

The Impact of PIK3R1 Mutations and Insulin-PI3K-Glycolytic Pathway Regulation in Prostate Cancer. | LitMetric

AI Article Synopsis

  • Over 40% of metastatic castration-resistant prostate cancer patients have changes in the PI3K/AKT pathway, mainly due to the loss of the PTEN gene, but the role of other components like PIK3R1 is not well understood.
  • This study analyzed tumor samples from over 1,400 prostate cancer cases and found that alterations in PIK3R1 were more common in metastatic cancers and linked to poorer survival outcomes across various cancer types.
  • PIK3R1 loss led to increased cell growth and activity in prostate cancer cells and made them more responsive to AKT inhibitors, highlighting its potential as a key player in cancer metabolism and treatment resistance.

Article Abstract

Purpose: Oncogenic alterations of the PI3K/AKT pathway occur in >40% of patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance of other PI3K pathway components in prostate cancer is largely unknown.

Experimental Design: Patients in this study underwent tumor sequencing using the MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; and structural rearrangements, or were profiled through The Cancer Genome Atlas. The association between PIK3R1 alteration/expression and survival was evaluated using univariable and multivariable Cox proportional-hazards regression models. We used the siRNA-based knockdown of PIK3R1 for functional studies. FDG-PET/CT examinations were performed with a hybrid positron emission tomography (PET)/CT scanner for some prostate cancer patients in the MSK-IMPACT cohort.

Results: Analyzing 1,417 human prostate cancers, we found a significant enrichment of PIK3R1 alterations in metastatic cancers compared with primary cancers. PIK3R1 alterations or reduced mRNA expression tended to be associated with worse clinical outcomes in prostate cancer, particularly in primary disease, as well as in breast, gastric, and several other cancers. In prostate cancer cell lines, PIK3R1 knockdown resulted in increased cell proliferation and AKT activity, including insulin-stimulated AKT activity. In cell lines and organoids, PIK3R1 loss/mutation was associated with increased sensitivity to AKT inhibitors. PIK3R1-altered patient prostate tumors had increased uptake of the glucose analogue 18F-fluorodeoxyglucose in PET imaging, suggesting increased glycolysis.

Conclusions: Our findings describe a novel genomic feature in metastatic prostate cancer and suggest that PIK3R1 alteration may be a key event for insulin-PI3K-glycolytic pathway regulation in prostate cancer.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438279PMC
http://dx.doi.org/10.1158/1078-0432.CCR-21-4272DOI Listing

Publication Analysis

Top Keywords

prostate cancer
32
prostate
10
cancer
9
insulin-pi3k-glycolytic pathway
8
pathway regulation
8
regulation prostate
8
pik3r1 alterations
8
cell lines
8
akt activity
8
pik3r1
7

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!