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Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival

Jessie M Vo1, Linh M La1, Ananda V Anderson1

  • 1Clinical and Experimental Therapeutics, University of Georgia, Augusta, Georgia, USA.

Physiological Reports
|January 5, 2025
PubMed

Insights

Genetic alterations in P21-activated kinases (PAKs) are linked to reduced patient survival in several cancers. PAKs show promise as predictive biomarkers and therapeutic targets, especially for metastatic disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Metastatic cancer presents significant treatment challenges due to a lack of reliable biomarkers and effective therapies.
  • P21-activated kinases (PAKs) are implicated in cancer progression, but their role as predictive markers and therapeutic targets remains under-investigated.
  • Genetic alterations in PAK isoforms may correlate with decreased patient survival.

Purpose of the Study:

  • To investigate the association between genetic alterations in PAK genes and overall patient survival.
  • To explore the potential of PAK isoforms as predictive biomarkers for metastasis.
  • To evaluate PAKs as therapeutic targets in various cancer types.

Main Methods:

  • Utilized data from the cBioPortal for Cancer Genomics.
  • Analyzed multiple randomized, multicentered phase-3 clinical trial datasets.
  • Examined genetic alterations and expression levels of PAK genes in relation to survival outcomes.

Main Results:

  • Significant genetic alterations in PAK genes were identified in breast, prostate, pancreatic, and lung cancers.
  • Elevated PAK expression correlated with poorer survival in prostate and breast cancer patients.
  • A trend towards poorer survival with PAK alterations was observed in pancreatic and lung cancers, though not statistically significant.

Conclusions:

  • PAKs are important potential biomarkers and therapeutic targets, particularly in metastatic cancers.
  • Targeted interventions in PAK-related pathways could improve patient outcomes.
  • PAKs may serve as reliable biomarkers for cancer diagnosis, monitoring, and personalized treatment strategies.
Keywords:
P21 activated kinasecancergenetic alterationsmetastasispatient survival

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