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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Apoptotic Signaling Across Breast Cancer Subtypes and Cryoablation-Induced Tissue Injury.

Agata Panfil1, Kacper Boroń2,3,4,5, Tomasz Sirek1,2,6

  • 1Collegium Medicum, WSB University, 41-300 Dąbrowa Górnicza, Poland.

International Journal of Molecular Sciences
|June 26, 2026
PubMed
Summary

Breast cancer progression shows altered apoptosis signaling, with reduced pro-apoptotic activity and increased stress adaptation in aggressive tumors. This contrasts with transient systemic responses observed after benign fibroadenoma cryoablation.

Keywords:
apoptosisbreast cancercell death regulationcryoablationmicroRNA

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Apoptosis is crucial for tissue homeostasis; its dysregulation drives breast cancer progression and therapeutic resistance.
  • Understanding apoptosis signaling across breast cancer subtypes is vital for targeted therapies.

Purpose of the Study:

  • To investigate apoptosis-related signaling patterns in breast cancer molecular subtypes.
  • To compare malignant apoptosis dysregulation with systemic responses to benign tissue injury (cryoablation).

Main Methods:

  • Integrative analysis of gene expression (mRNA microarrays, qRT-PCR) and protein levels (ELISA) in breast cancer tissues.
  • Assessment of apoptosis pathway activity using MSigDB HALLMARK_APOPTOSIS gene set, intrinsic/extrinsic pathway scoring, and apoptotic balance index (ABI).
  • MicroRNA profiling and in silico analyses to identify miRNA-mRNA interactions.

Main Results:

  • Aggressive breast cancers exhibit reduced pro-apoptotic signaling and increased stress-adaptive responses, particularly in triple-negative and HER2-positive subtypes.
  • Key findings include decreased intrinsic pathway activity, lower ABI, downregulation of pro-apoptotic genes (BIK, BMF, TXNIP), and upregulation of stress genes (HSPB1, PPT1).
  • Overexpression of specific miRNAs (e.g., miR-582-5p, miR-421) correlated with apoptosis-related gene expression changes.

Conclusions:

  • Breast cancer malignancy is characterized by distinct apoptosis pathway dysregulation compared to the transient systemic responses seen after benign fibroadenoma cryoablation.
  • Findings identify potential molecular networks (miRNA-mRNA interactions) involved in breast cancer progression and therapeutic resistance.
  • Pathway-level interpretation highlights differences between malignant dysregulation and regulated physiological responses.