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Peer-reviewedCC BY 4.0Cells

Cervical and Breast Cancer: Uncontrolled Epithelial Growth Driven by Xenoestrogen Dominance, Disrupted Paracrine Signaling, and Arrested Apoptosis

  • Albert Despot1
  • Ivan Sabol2
  • Zlatko Hrgović3
  • Ana-Marija Despot4
  • Ivica Vlatkovic5
  • Mara Tešanović6
  • Dora Fureš7
  • Sanja Malinac Malojčić8,9
  • Vesna Ćosić9,10
  • Nikola Sinković11
  • Rajko Fureš8,9,12
12 affiliations
  1. 1Clinic for Gynecology and Obstetrics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
  2. 2Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia
  3. 3Goethe University, 60629 Frankfurt am Main, Germany
  4. 4Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, Croatia
  5. 5Gynecology Practice Dr Vlatković, 23000 Zadar, Croatia
  6. 6Department of Obstetrics and Gynecology, Dubrovnik General Hospital, 20000 Dubrovnik, Croatia
  7. 7Department of Neurology, Zabok General Hospital and Croatian Veterans Hospital, 49210 Zabok, Croatia
  8. 8Department of Obstetrics and Gynecology, Zabok General Hospital and Croatian Veterans Hospital, 49210 Zabok, Croatia
  9. 9Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
  10. 10Polyclinic Cosic, 35000 Slavonski Brod, Croatia
  11. 11Croatian Society of Pelviperineology, 49210 Zabok, Croatia
  12. 12Faculty of Health Studies, University of Rijeka, 51000 Rijeka, Croatia
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Abstract

Cervical cancer and breast cancer represent two serious challenges in modern gynecological oncology. Despite their anatomical accessibility for screening, significant investments in research, and the development of therapeutic strategies, their global incidence and mortality rates continue to rise. Interstitial spaces, paracrine signaling, hormonal imbalance linked to xenoestrogens (XE) and the consequent inhibition of apoptosis constitute a common, yet unfortunately insufficiently recognized, link in the carcinogenesis of both cervical and breast cancer. The aim of this paper is to supplement the classical paradigm of cervical and breast carcinogenesis by incorporating a broader context currently missing from the understanding of both forms of cancer. XEs are widely distributed chemical substances, found in a wide range of everyday products, food and environment, that mimic the action of endogenous estrogen. In the world of basic science, the connection between estrogen dominance and apoptosis avoidance is unquestionable and can undeniably impact progression of breast and cervical cancer. In the development of breast cancer, the association between XE facilitated estrogen dominance and arrested apoptosis is of great importance. In the pathogenesis of cervical cancer, the activity of viral oncogenes E6/E7 is the main driver of the pathological condition; however, in the context of arrested apoptosis, there is an area of overlap between estrogen dominance and HPV virus action. In this sense, estrogen dominance, triggered by the agonistic action of XEs on the membrane-bound GPER receptor of fibroblasts, is a cofactor in cervical carcinogenesis that remains insufficiently researched.

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Cite

BibTeXRIS
BibTeX
@article{despot2026cervical,
  title = {{Cervical and Breast Cancer: Uncontrolled Epithelial Growth Driven by Xenoestrogen Dominance, Disrupted Paracrine Signaling, and Arrested Apoptosis}},
  author = {Albert Despot and Ivan Sabol and Zlatko Hrgović and Ana-Marija Despot and Ivica Vlatkovic and Mara Tešanović and Dora Fureš and Sanja Malinac Malojčić and Vesna Ćosić and Nikola Sinković and Rajko Fureš},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15211956},
  url = {https://www.mdpi.com/2073-4409/15/21/1956},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Cervical and Breast Cancer: Uncontrolled Epithelial Growth Driven by Xenoestrogen Dominance, Disrupted Paracrine Signaling, and Arrested Apoptosis
AU  - Albert Despot
AU  - Ivan Sabol
AU  - Zlatko Hrgović
AU  - Ana-Marija Despot
AU  - Ivica Vlatkovic
AU  - Mara Tešanović
AU  - Dora Fureš
AU  - Sanja Malinac Malojčić
AU  - Vesna Ćosić
AU  - Nikola Sinković
AU  - Rajko Fureš
PY  - 2026
DA  - 2026/10/27
JO  - Cells
DO  - 10.3390/cells15211956
UR  - https://www.mdpi.com/2073-4409/15/21/1956
AB  - Cervical cancer and breast cancer represent two serious challenges in modern gynecological oncology. Despite their anatomical accessibility for screening, significant investments in research, and the development of therapeutic strategies, their global incidence and mortality rates continue to rise. Interstitial spaces, paracrine signaling, hormonal imbalance linked to xenoestrogens (XE) and the consequent inhibition of apoptosis constitute a common, yet unfortunately insufficiently recognized, link in the carcinogenesis of both cervical and breast cancer. The aim of this paper is to supplement the classical paradigm of cervical and breast carcinogenesis by incorporating a broader context currently missing from the understanding of both forms of cancer. XEs are widely distributed chemical substances, found in a wide range of everyday products, food and environment, that mimic the action of endogenous estrogen. In the world of basic science, the connection between estrogen dominance and apoptosis avoidance is unquestionable and can undeniably impact progression of breast and cervical cancer. In the development of breast cancer, the association between XE facilitated estrogen dominance and arrested apoptosis is of great importance. In the pathogenesis of cervical cancer, the activity of viral oncogenes E6/E7 is the main driver of the pathological condition; however, in the context of arrested apoptosis, there is an area of overlap between estrogen dominance and HPV virus action. In this sense, estrogen dominance, triggered by the agonistic action of XEs on the membrane-bound GPER receptor of fibroblasts, is a cofactor in cervical carcinogenesis that remains insufficiently researched.
SN  - 2073-4409
ER  -