Molecular Approaches to Gynecological Cancers: Biomarkers and Targeted Therapeutic Pathways

Öz

Gynecological cancers, including ovarian, endometrial, and cervical malignancies, represent a heterogeneous group of tumors characterized by distinct clinical behaviors and complex molecular properties. Advances in molecular oncology have substantially reshaped the understanding of gynecological carcinogenesis, revealing that dysregulation of tumor suppressor genes, DNA damage repair pathways, oncogenic signaling cascades, and virus-driven mechanisms critically influence disease initiation, progression, and therapeutic response. In ovarian cancer, alterations in homologous recombination repair, TP53 mutations, and aberrant activation of MAPK and PI3K/AKT signaling pathways have enabled molecular stratification and the successful implementation of targeted therapies. Endometrial cancer exemplifies the transition toward molecular classification, with POLE exonuclease domain mutations, mismatch repair deficiency, and copy number alterations defining biologically and clinically distinct subgroups with divergent prognostic outcomes. Cervical cancer represents a unique virus associated malignancy in which persistent high risk human papillomavirus infection drives oncogenesis through disruption of cell cycle regulatory pathways, providing a robust biological basis for molecular diagnostics and prevention strategies. This review comprehensively summarizes the current knowledge of key molecular biomarkers and signaling pathways involved in gynecological cancers, including CA-125, mismatch repair deficiency, TP53, HER2, BRCA-associated DNA repair mechanisms, POLE mutations, WNT/β-catenin signaling, and HPV-related molecular alterations. Furthermore, the clinical implications of these molecular insights for diagnosis, prognosis, risk stratification, and personalized therapeutic approaches are discussed. In conclusion, integration of molecular profiling into clinical practice represents a critical step toward precision medicine in gynecological oncology, offering the potential to improve patient outcomes through biomarker-driven diagnosis and targeted treatment strategies.

Anahtar Kelimeler

• Gynecological cancers
• Ovarian cancer
• Endometrial cancer
• Cervical cancer
• Targeted therapy
• Molecular biomarkers

Jinekolojik Kanserlere Moleküler Yaklaşımlar: Biyobelirteçler ve Hedefli Tedavi Yolları

Öz

Yumurtalık, endometriyum ve servikal maligniteler de dahil olmak üzere jinekolojik kanserler, farklı klinik davranışlar ve karmaşık moleküler özelliklerle karakterize edilen heterojen bir tümör grubudur. Moleküler onkolojideki gelişmeler, jinekolojik karsinogenezin anlaşılmasını önemli ölçüde yeniden şekillendirmiş ve tümör baskılayıcı genlerin düzensizliğinin, DNA hasar onarım yollarının, onkojenik sinyal kaskadlarının ve virüs kaynaklı mekanizmaların hastalık başlangıcını, ilerlemesini ve tedaviye yanıtı kritik olarak etkilediğini ortaya koymuştur. Yumurtalık kanserinde, homolog rekombinasyon onarımındaki değişiklikler, TP53 mutasyonları, MAPK ve PI3K/AKT sinyal yollarının anormal aktivasyonu, moleküler sınıflandırmayı ve hedefe yönelik tedavilerin başarılı bir şekilde uygulanmasını sağlamıştır. Endometriyum kanseri, POLE eksonükleaz mutasyonları, yanlış eşleşme tamir mekanizma eksikliği ve kopya sayısı değişiklikleri ile biyolojik ve klinik olarak farklı alt grupları tanımlayan ve farklı prognostik sonuçlara sahip moleküler sınıflandırmayı temsil etmektedir. Servikal kanser, kalıcı yüksek riskli insan papillomavirüsü enfeksiyonunun hücre döngüsü düzenleyici yollarının bozulmasıyla onkogenezi tetiklediği, virüsle ilişkili maligniteyi temsil eder ve moleküler tanı, önleme stratejileri için biyolojik temeli oluşturur. Bu derleme, CA-125, yanlış eşleşme tamir mekanizması, TP53, HER2, BRCA ile ilişkili DNA onarım mekanizmaları, POLE mutasyonları, WNT/β-katenin sinyallemesi ve HPV ile ilgili moleküler değişiklikler de dahil olmak üzere jinekolojik kanserlerde yer alan temel moleküler biyobelirteçler ve sinyal yolları hakkındaki mevcut bilgileri kapsamlı bir şekilde özetlemektedir. Ayrıca, bu moleküler bilgilerin tanı, prognoz, risk sınıflandırması ve kişiselleştirilmiş tedavi yaklaşımları için klinik etkileri tartışılmaktadır. Sonuç olarak, moleküler profillemenin klinik uygulamaya entegrasyonu, jinekolojik onkolojide hassas tıbba doğru kritik bir adımı temsil etmekte ve biyobelirteç odaklı tanı ve hedefli tedavi stratejileri yoluyla hasta sonuçlarını iyileştirme potansiyeli sunmaktadır.

Anahtar Kelimeler

• Jinekolojik kanserler
• Yumurtalık kanseri
• Endometrium kanseri
• Rahim ağzı kanseri
• Hedefli tedavi
• Moleküler biyobelirteçler

Kaynakça

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