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International Journal of Integrative and Modern Medicine

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Molecular Pathways Underlying the Pathogenesis of Triple-Negative Breast Cancer

Vol. 3 No. 9 (2025): International Journal of Integrative and Modern Medicine:
Published : Sep 30, 2025

Khаkimоv Gоlib Аbdullауеviсh (1), Аlmurаdоvа Dilbаr Murаdоvnа (2), Kholiddinov Khumoyunmirzo Shukhratjon ugli (3), Otaboyeva Maftuna Mahmud kizi (4), Abdirimov Komiljon Xasanovich (5)

(1) Рrоf. MD Hеаd оf dераrtmеnt оf оnсоlоgу, реdiаtric оncоlоgу аnd раlliаtivе cаrе. Tаshkеnt Stаtе Mеdiсаl Univеrsitу, Tаshkеnt, Uzbеkistаn, Uzbekistan
(2) РhD, Аssосiаtе рrоfеssоr оf Dераrtmеnt оf Оnсоlоgу, реdiаtric оncоlоgу аnd раlliаtivе cаrе. Tаshkеnt Stаtе Mеdiсаl Univеrsitу, Tаshkеnt, Uzbеkistаn, Uzbekistan
(3) Master оf dераrtmеnt оf оnсоlоgу, реdiаtric оncоlоgу аnd раlliаtivе cаrе. Tаshkеnt Stаtе Mеdiсаl Univеrsitу , Tаshkеnt, Uzbеkistаn, Uzbekistan
(4) Master оf dераrtmеnt оf оnсоlоgу, реdiаtric оncоlоgу аnd раlliаtivе cаrе. Tаshkеnt Stаtе Mеdiсаl Univеrsitу , Tаshkеnt, Uzbеkistаn, Uzbekistan
(5) Master оf dераrtmеnt оf оnсоlоgу, реdiаtric оncоlоgу аnd раlliаtivе cаrе. Tаshkеnt Stаtе Mеdiсаl Univеrsitу , Tаshkеnt, Uzbеkistаn, Uzbekistan
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Abstract:

Breast cancer remains the most prevalent malignancy among women worldwide, with triple-negative breast cancer (TNBC) representing one of its most aggressive and clinically challenging subtypes. TNBC, defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, accounts for 10–15% of all breast cancers but contributes disproportionately to global mortality. The pathogenesis of TNBC is driven by multiple genetic and molecular alterations, including BRCA1/2 and TP53 mutations, PTEN loss, and homologous recombination deficiency (HRD), which promote genomic instability. Epigenetic dysregulation, such as aberrant DNA methylation and non-coding RNA alterations, further contributes to tumor progression and immune evasion. Additionally, the activation of oncogenic signaling pathways—including PI3K/Akt/mTOR, Notch, Wnt/β-catenin, and JAK/STAT—enhances cell proliferation, epithelial–mesenchymal transition, and drug resistance. These molecular features not only underscore TNBC’s heterogeneity and poor prognosis but also highlight novel therapeutic opportunities, such as PARP inhibitors, epigenetic therapies, and pathway-specific targeted agents. Addressing TNBC is especially critical in regions with limited screening and treatment access, such as Central Asia and Uzbekistan, where late diagnosis and restricted availability of advanced therapeutics exacerbate poor clinical outcomes.

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