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Basic molecular mechanisms effective in the development of gynecological cancers

Yıl 2024, Cilt: 24 Sayı: 3, 137 - 148

Öz

Cancers occur due to an imbalance between cell proliferation, development, and death. Carcinogenesis is the process of turning a normal cell into a cancer cell that divides uncontrollably by genetic deterioration. It has been understood that various molecular mechanisms play a role not only in carcinogenesis but also in metastasis formation and treatment sensitivity. Various mutations have been detected in proto-oncogenes, tumor suppressor genes, or DNA repair genes, which have important functions in the cell cycle in most malignant tumors. Since most cancer cells are genetically unstable, mutations that lead to aggressive behavior such as invasion and metastasis accumulate during carcinogenesis. The presence of these molecular changes allows the development of different treatment options for tumors, called targeted or tailored therapy. In addition, options that will contribute to differential diagnosis and treatment can be created by evaluating tumor mutation burden, microsatellite instability, and homologous recombination deficiency in tumors. Compared to other areas of oncology, gynecological oncology is one of the areas where genetics-based personalized medical treatments are weakest. In this review, the molecular mechanisms effective in the development of gynecological cancers detected to date, the effectiveness of drugs used in treatment, and new targeted treatment options that can be used in treatment are examined.

Proje Numarası

YOK

Kaynakça

  • Şahin F. Jinekolojik kanserlerde genetik. Türk jinekolojik onkoloji dergisi 2009; 12(1), 1-9.
  • Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ 2022; 29(5): 946-960. doi: 10.1038/s41418-022-00988-z.
  • Diniz G. Temel kavramlar: DNA hasarı-DNA onarımı-instabilite. Eds: Aktaş S, Alakavuklar M. Klinis-yenler İçin Temel Onkoloji. 1. Baskı. Ankara: Türkiye Klinikleri; 2021. p.14- 22.
  • Tok F, Koçyiğit Kaymakçıoğlu B. Kanser tedavisinde yeni bir yaklaşım: Poli (ADP-riboz) polimeraz-1 inhibitörleri. Clinical and Experimental Health Sciences 2015; 5(1): 41-52. Doi: 10.5455/musbed.20141015015238
  • Ali A, Li X. Oncogenic Molecular Pathways: Mechanisms, Mutations and Inhibitors. Ann Hematol Oncol 2016; 3(8): 1108.
  • Song Y, Pan S, Li K, Chen X, Wang ZP, Zhu X. Insight into the role of multiple signaling pathways in regulating cancer stem cells of gynecologic cancers, Seminars in Cancer Biology 2022; 85: 219-233. Doi: 10.1016/j.semcancer.2021.06.001.
  • Brasseur K, Gévry N, Asselin E. Chemoresistance and targeted therapies in ovarian and endometrial cancers. Oncotarget 2017; 8(3): 4008-4042. doi: 10.18632/oncotarget.14021.
  • Burmeister CA, Khan SF, Schäfer G, Mbatani N, Adams T, Moodley J, Prince S. Cervical cancer the-rapies: Current challenges and future perspectives. Tumour Virus Res 2022;13:200238. doi: 10.1016/j.tvr.2022.200238.
  • Badr RE, Walts AE, Chung F, Bose S. BD ProEx C: a sensitive and specific marker of HPV-associated squamous lesions of the cervix. Am J Surg Pathol. 2008;32(6):899-906. doi: 10.1097/PAS.0b013e31815bbb69.
  • Sun H, Shen K, Cao D. Progress in immunocytochemical staining for cervical cancer screening. Can-cer Manag Res. 2019;11:1817-1827. DOI: 10.2147/CMAR.S195349.
  • Li M, Yang J, Liu K, Yang J, Zhan X, Wang L, Shen X, Chen J, Mao Z. p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis. J Cancer. 2020;11(6):1457-1467. doi: 10.7150/jca.35479.
  • Lubowicka, E., Zbucka-Kretowska, M., Sidorkiewicz, I. et al. Diagnostic Power of Cytokine M-CSF, Metalloproteinase 2 (MMP-2) and Tissue Inhibitor-2 (TIMP-2) in Cervical Cancer Patients Based on ROC Analysis. Pathol Oncol Res 2020; 26, 791–800 Doi: 10.1007/s12253-019-00626-z
  • Priyanka D, Arunachalam S, Amitkumar K, John JJ, Sudalaimuthu M. An Immunohistochemical Study on Ki-67 Expression in Squamous Cell Carcinomas of Cervix With Clinicopathological Correlation. Cureus 2023;15(1):e34155. doi: 10.7759/cureus.34155.
  • Shi Q, Xu L, Yang R, Meng Y, Qiu L. Ki-67 and P16 proteins in cervical cancer and precancerous lesi-ons of young women and the diagnostic value for cervical cancer and precancerous lesions. Oncol Lett 2019;18(2):1351-1355. doi: 10.3892/ol.2019.10430.
  • Ding L, Song L, Zhao W, Li X, Gao W, Qi Z and Wang J. Predictive value of p16INK4a, Ki‑67 and ProExC immuno‑qualitative features in LSIL progression into HSIL. Exp Ther Med 2020; 19: 2457-2466.
  • Wang P-H, Ko J-L, Yang S-F, et al. Significant Relation of Tissue Inhibitor of Matrix Metalloprotei-nase-2 and Its Combination With Matrix Metalloproteinase-2 to Survival of Patients With Cancer of Uterine Cervix. Reproductive Sciences 2011;18(8):798-808. doi:10.1177/1933719111398143.
  • Chen W, Huang S, Shi K, Yi L, Liu Y, Liu W. Prognostic Role of Matrix Metalloproteinases in Cervical Cancer: A Meta-Analysis. Cancer Control. 2021;28:10732748211033743. doi: 10.1177/10732748211033743.
  • Caserta, D.; De Marco, M.P.; Besharat, A.R.; Costanzi, F. Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review. Int. J. Mol. Sci. 2022, 23, 2956. https://doi.org/10.3390/ijms23062956
  • Berg, H.F., Engerud, H., Myrvold, M. et al. Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value. Br J Cancer 2023; 128, 647–655 (2023). https://doi.org/10.1038/s41416-022-02063-3
  • Vermij L, Horeweg N, Leon-Castillo A, Rutten TA, Mileshkin LR, Mackay HJ, Leary A, Powell ME, Singh N, Crosbie EJ, et al. HER2 Status in High-Risk Endometrial Cancers (PORTEC-3): Relationship with Histotype, Molecular Classification, and Clinical Outcomes. Cancers. 2021; 13(1):44. https://doi.org/10.3390/cancers13010044.
  • Margul D, Yu C, AlHilli MM. Tumor Immune Microenvironment in Gynecologic Cancers. Cancers. 2023; 15(15):3849. https://doi.org/10.3390/cancers15153849
  • Zhang, B., Chen, F., Xu, Q. et al. Revisiting ovarian cancer microenvironment: a friend or a foe?. Protein Cell 9, 674–692 (2018). https://doi.org/10.1007/s13238-017-0466-7
  • Diniz G, Yaşın Y, Çoban C, Evcimen Ş, Karakayalı M. Bağışıklık Sistemi: Güvenilir Bir Dost mu, İşbirlik-çi Bir Düşman mı? Forbes Tıp Dergisi 2022; 3(1): 1-9. Doi: 10.4274/forbes.galenos.2021.30974.
  • Solakoglu Kahraman D, Diniz G, Sayhan S, Sayar C, Ayaz D, Gokcu M, Karadeniz T. The prognostic significance of pdl1 and foxp3 expressions in tumor cells and the tumor microenvironment of ova-rian epithelial tumors. Int J Clin Exp Pathol 2018; 11(8): 3884–3890.
  • GeorgesA, Auguste A, Bessie`re L, Vanet A. Todeschini AL, Veitia RA. FOXL2: A central transcription factor of the ovary. Journal of Molecular Endocrinology 2014; 52(1): R17–R33. DOI: 10.1530/JME-13-0159.
  • Han LM, Weiel JJ, Longacre TA, Folkins AK. DICER1-associated Tumors in the Female Genital Tract: Molecular Basis, Clinicopathologic Features, and Differential Diagnosis. Advances In Anatomic Pat-hology 2022; 29(5): 297-308. DOI: 10.1097/PAP.0000000000000351
  • McAlpine JN, Chiu DS, Nout RA, Church DN, Schmidt P, Lam S, et al. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis. Cancer 2021; 127(14): 2409-2422. Doi: 10.1002/cncr.33516.
  • D Ayaz, G Diniz, S Sayhan, O Kaya, DS Kahraman, T Karadeniz, M Sanci. The clinicopathologic signifi-cance of the ARID1A expression in ovarian epithelial tumors. EJGO 2019; 40 (4): 567-571. Doi: 10.12892/ejgo4467.2019.
  • Wu, Y., Xu, S., Cheng, S. et al. Clinical application of PARP inhibitors in ovarian cancer: from mole-cular mechanisms to the current status. J Ovarian Res 16, 6 (2023). https://doi.org/10.1186/s13048-023-01094-5.

Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar

Yıl 2024, Cilt: 24 Sayı: 3, 137 - 148

Öz

Kanserler hücrelerin çoğalma, gelişme ve ölümü arasındaki denge bozukluğuna bağlı ortaya çıkarlar. Normal bir hücrenin genetiğinin bozulması ile kontrolsüz bir şekilde bölünen kanser hücresine dönüşme süreci karsinogenez olarak adlandırılır. Salt karsinogenezde değil, metastaz oluşumu ve tedavi duyarlılığında da çeşitli moleküler mekanizmaların rol oynadığı anlaşılmıştır. Malign tümörlerin çoğunda hücre siklusunda önemli işlevleri olan protoonkogenler, tümör supresör genleri veya DNA tamir genlerinde çeşitli mutasyonlar saptanmıştır. Çoğu kanser hücresi genetik olarak kararsız olduğundan invazyon ve metastaz gibi agresif davranışlara yol açan mutasyonlar da karsinogenez süresince birikmektedir. Söz konusu moleküler değişikliklerin varlığı tümörler için hedefe yönelik veya kişiselleştirilmiş tedavi denilen farklı tedavi seçenekleri geliştirilmesine olanak vermektedir. Ayrıca tümörlerde, tümör mutasyon yükü, mikrosatellit kararsızlığı ve homolog rekombinasyon eksikliğinin değerlendirilmesiyle de ayırıcı tanı ve tedaviye katkı sağlayacak seçenekler yaratılabilmektedir. Onkolojinin diğer alanlarıyla karşılaştırıldığında jinekolojik onkoloji, genetiğe dayalı kişiselleştirilmiş tıbbı tedavilerin en zayıf kaldığı alanlardan biridir. Bu derlemede günümüze dek saptanan jinekolojik kanserlerin gelişmesinde etkili moleküler mekanizmalar, tedavide kullanılan ilaçların etkinliği ve tedavide kullanılabilecek yeni hedefe yönelik tedavi seçenekleri irdelenmiştir.

Etik Beyan

Derlemenin yazımında çıkar çatışması yoktur.

Destekleyen Kurum

YOK

Proje Numarası

YOK

Teşekkür

YOK

Kaynakça

  • Şahin F. Jinekolojik kanserlerde genetik. Türk jinekolojik onkoloji dergisi 2009; 12(1), 1-9.
  • Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ 2022; 29(5): 946-960. doi: 10.1038/s41418-022-00988-z.
  • Diniz G. Temel kavramlar: DNA hasarı-DNA onarımı-instabilite. Eds: Aktaş S, Alakavuklar M. Klinis-yenler İçin Temel Onkoloji. 1. Baskı. Ankara: Türkiye Klinikleri; 2021. p.14- 22.
  • Tok F, Koçyiğit Kaymakçıoğlu B. Kanser tedavisinde yeni bir yaklaşım: Poli (ADP-riboz) polimeraz-1 inhibitörleri. Clinical and Experimental Health Sciences 2015; 5(1): 41-52. Doi: 10.5455/musbed.20141015015238
  • Ali A, Li X. Oncogenic Molecular Pathways: Mechanisms, Mutations and Inhibitors. Ann Hematol Oncol 2016; 3(8): 1108.
  • Song Y, Pan S, Li K, Chen X, Wang ZP, Zhu X. Insight into the role of multiple signaling pathways in regulating cancer stem cells of gynecologic cancers, Seminars in Cancer Biology 2022; 85: 219-233. Doi: 10.1016/j.semcancer.2021.06.001.
  • Brasseur K, Gévry N, Asselin E. Chemoresistance and targeted therapies in ovarian and endometrial cancers. Oncotarget 2017; 8(3): 4008-4042. doi: 10.18632/oncotarget.14021.
  • Burmeister CA, Khan SF, Schäfer G, Mbatani N, Adams T, Moodley J, Prince S. Cervical cancer the-rapies: Current challenges and future perspectives. Tumour Virus Res 2022;13:200238. doi: 10.1016/j.tvr.2022.200238.
  • Badr RE, Walts AE, Chung F, Bose S. BD ProEx C: a sensitive and specific marker of HPV-associated squamous lesions of the cervix. Am J Surg Pathol. 2008;32(6):899-906. doi: 10.1097/PAS.0b013e31815bbb69.
  • Sun H, Shen K, Cao D. Progress in immunocytochemical staining for cervical cancer screening. Can-cer Manag Res. 2019;11:1817-1827. DOI: 10.2147/CMAR.S195349.
  • Li M, Yang J, Liu K, Yang J, Zhan X, Wang L, Shen X, Chen J, Mao Z. p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis. J Cancer. 2020;11(6):1457-1467. doi: 10.7150/jca.35479.
  • Lubowicka, E., Zbucka-Kretowska, M., Sidorkiewicz, I. et al. Diagnostic Power of Cytokine M-CSF, Metalloproteinase 2 (MMP-2) and Tissue Inhibitor-2 (TIMP-2) in Cervical Cancer Patients Based on ROC Analysis. Pathol Oncol Res 2020; 26, 791–800 Doi: 10.1007/s12253-019-00626-z
  • Priyanka D, Arunachalam S, Amitkumar K, John JJ, Sudalaimuthu M. An Immunohistochemical Study on Ki-67 Expression in Squamous Cell Carcinomas of Cervix With Clinicopathological Correlation. Cureus 2023;15(1):e34155. doi: 10.7759/cureus.34155.
  • Shi Q, Xu L, Yang R, Meng Y, Qiu L. Ki-67 and P16 proteins in cervical cancer and precancerous lesi-ons of young women and the diagnostic value for cervical cancer and precancerous lesions. Oncol Lett 2019;18(2):1351-1355. doi: 10.3892/ol.2019.10430.
  • Ding L, Song L, Zhao W, Li X, Gao W, Qi Z and Wang J. Predictive value of p16INK4a, Ki‑67 and ProExC immuno‑qualitative features in LSIL progression into HSIL. Exp Ther Med 2020; 19: 2457-2466.
  • Wang P-H, Ko J-L, Yang S-F, et al. Significant Relation of Tissue Inhibitor of Matrix Metalloprotei-nase-2 and Its Combination With Matrix Metalloproteinase-2 to Survival of Patients With Cancer of Uterine Cervix. Reproductive Sciences 2011;18(8):798-808. doi:10.1177/1933719111398143.
  • Chen W, Huang S, Shi K, Yi L, Liu Y, Liu W. Prognostic Role of Matrix Metalloproteinases in Cervical Cancer: A Meta-Analysis. Cancer Control. 2021;28:10732748211033743. doi: 10.1177/10732748211033743.
  • Caserta, D.; De Marco, M.P.; Besharat, A.R.; Costanzi, F. Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review. Int. J. Mol. Sci. 2022, 23, 2956. https://doi.org/10.3390/ijms23062956
  • Berg, H.F., Engerud, H., Myrvold, M. et al. Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value. Br J Cancer 2023; 128, 647–655 (2023). https://doi.org/10.1038/s41416-022-02063-3
  • Vermij L, Horeweg N, Leon-Castillo A, Rutten TA, Mileshkin LR, Mackay HJ, Leary A, Powell ME, Singh N, Crosbie EJ, et al. HER2 Status in High-Risk Endometrial Cancers (PORTEC-3): Relationship with Histotype, Molecular Classification, and Clinical Outcomes. Cancers. 2021; 13(1):44. https://doi.org/10.3390/cancers13010044.
  • Margul D, Yu C, AlHilli MM. Tumor Immune Microenvironment in Gynecologic Cancers. Cancers. 2023; 15(15):3849. https://doi.org/10.3390/cancers15153849
  • Zhang, B., Chen, F., Xu, Q. et al. Revisiting ovarian cancer microenvironment: a friend or a foe?. Protein Cell 9, 674–692 (2018). https://doi.org/10.1007/s13238-017-0466-7
  • Diniz G, Yaşın Y, Çoban C, Evcimen Ş, Karakayalı M. Bağışıklık Sistemi: Güvenilir Bir Dost mu, İşbirlik-çi Bir Düşman mı? Forbes Tıp Dergisi 2022; 3(1): 1-9. Doi: 10.4274/forbes.galenos.2021.30974.
  • Solakoglu Kahraman D, Diniz G, Sayhan S, Sayar C, Ayaz D, Gokcu M, Karadeniz T. The prognostic significance of pdl1 and foxp3 expressions in tumor cells and the tumor microenvironment of ova-rian epithelial tumors. Int J Clin Exp Pathol 2018; 11(8): 3884–3890.
  • GeorgesA, Auguste A, Bessie`re L, Vanet A. Todeschini AL, Veitia RA. FOXL2: A central transcription factor of the ovary. Journal of Molecular Endocrinology 2014; 52(1): R17–R33. DOI: 10.1530/JME-13-0159.
  • Han LM, Weiel JJ, Longacre TA, Folkins AK. DICER1-associated Tumors in the Female Genital Tract: Molecular Basis, Clinicopathologic Features, and Differential Diagnosis. Advances In Anatomic Pat-hology 2022; 29(5): 297-308. DOI: 10.1097/PAP.0000000000000351
  • McAlpine JN, Chiu DS, Nout RA, Church DN, Schmidt P, Lam S, et al. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis. Cancer 2021; 127(14): 2409-2422. Doi: 10.1002/cncr.33516.
  • D Ayaz, G Diniz, S Sayhan, O Kaya, DS Kahraman, T Karadeniz, M Sanci. The clinicopathologic signifi-cance of the ARID1A expression in ovarian epithelial tumors. EJGO 2019; 40 (4): 567-571. Doi: 10.12892/ejgo4467.2019.
  • Wu, Y., Xu, S., Cheng, S. et al. Clinical application of PARP inhibitors in ovarian cancer: from mole-cular mechanisms to the current status. J Ovarian Res 16, 6 (2023). https://doi.org/10.1186/s13048-023-01094-5.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Jinekolojik Onkoloji Cerrahisi
Bölüm Derleme
Yazarlar

Gulden Diniz 0000-0003-1512-7584

Selçuk Erkılınç 0000-0002-6512-9070

Umut Varol 0000-0002-4669-2052

Proje Numarası YOK
Erken Görünüm Tarihi 31 Aralık 2024
Yayımlanma Tarihi
Gönderilme Tarihi 1 Ocak 2024
Kabul Tarihi 26 Ağustos 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 24 Sayı: 3

Kaynak Göster

APA Diniz, G., Erkılınç, S., & Varol, U. (2024). Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar. Türk Jinekolojik Onkoloji Dergisi, 24(3), 137-148.
AMA Diniz G, Erkılınç S, Varol U. Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar. TRSGO Dergisi. Aralık 2024;24(3):137-148.
Chicago Diniz, Gulden, Selçuk Erkılınç, ve Umut Varol. “Jinekolojik Kanserlerin gelişiminde Etkili Temel moleküler Mekanizmalar”. Türk Jinekolojik Onkoloji Dergisi 24, sy. 3 (Aralık 2024): 137-48.
EndNote Diniz G, Erkılınç S, Varol U (01 Aralık 2024) Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar. Türk Jinekolojik Onkoloji Dergisi 24 3 137–148.
IEEE G. Diniz, S. Erkılınç, ve U. Varol, “Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar”, TRSGO Dergisi, c. 24, sy. 3, ss. 137–148, 2024.
ISNAD Diniz, Gulden vd. “Jinekolojik Kanserlerin gelişiminde Etkili Temel moleküler Mekanizmalar”. Türk Jinekolojik Onkoloji Dergisi 24/3 (Aralık 2024), 137-148.
JAMA Diniz G, Erkılınç S, Varol U. Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar. TRSGO Dergisi. 2024;24:137–148.
MLA Diniz, Gulden vd. “Jinekolojik Kanserlerin gelişiminde Etkili Temel moleküler Mekanizmalar”. Türk Jinekolojik Onkoloji Dergisi, c. 24, sy. 3, 2024, ss. 137-48.
Vancouver Diniz G, Erkılınç S, Varol U. Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar. TRSGO Dergisi. 2024;24(3):137-48.