TY - JOUR
T1 - Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review
AU - Binju, Mudra
AU - Padilla, Monica Amaya
AU - Singomat, Terence
AU - Kaur, Pritinder
AU - Suryo Rahmanto, Yohan
AU - Cohen, Paul A.
AU - Yu, Yu
N1 - Funding Information:
This study was supported by the Raine Medical Research Foundation Priming Grant , RPG101-18 , Australia (Y.Y.).
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2
Y1 - 2019/2
N2 - Background: Advanced epithelial ovarian cancer is one of the hardest human malignancies to treat. Standard treatment involves cytoreductive surgery and platinum-based chemotherapy, however, median progression-free survival for patients diagnosed with advanced stage disease (FIGO stages III and IV) is approximately 18 months. There has been little improvement in overall survival over the past decade and less than half of women with advanced stage disease will be living 5 years after diagnosis. A majority of patients initially have a favourable response to platinum-based chemotherapy, but most will eventually relapse and their disease will become platinum resistant. Scope of review: Here, we review our current understanding of mechanisms that promote recurrence and acquired resistance in epithelial ovarian cancer with particular focus on studies that describe differences observed between untreated primary tumors and recurrent tumors, post-first-line chemotherapy. Multiple molecular mechanisms contribute to recurrence in patients following initial treatment for advanced epithelial ovarian cancer including those involving the tumor microenvironment, tumor immune status, cancer stem cells, DNA repair/cell survival pathways and extracellular matrix. Major conclusions: Due to the adaptive nature of recurrent tumors, the major contributing and specific resistance pattern may largely depend on the nature of the primary tumor itself. General significance: Future work that aims to elucidate the complex pattern of acquired resistance will be useful for predicting chemotherapy response/recurrence following primary diagnosis and to develop novel treatment strategies to improve the survival of patients with advanced epithelial ovarian cancer, especially in tumors not harbouring homologous DNA recombination repair deficiencies.
AB - Background: Advanced epithelial ovarian cancer is one of the hardest human malignancies to treat. Standard treatment involves cytoreductive surgery and platinum-based chemotherapy, however, median progression-free survival for patients diagnosed with advanced stage disease (FIGO stages III and IV) is approximately 18 months. There has been little improvement in overall survival over the past decade and less than half of women with advanced stage disease will be living 5 years after diagnosis. A majority of patients initially have a favourable response to platinum-based chemotherapy, but most will eventually relapse and their disease will become platinum resistant. Scope of review: Here, we review our current understanding of mechanisms that promote recurrence and acquired resistance in epithelial ovarian cancer with particular focus on studies that describe differences observed between untreated primary tumors and recurrent tumors, post-first-line chemotherapy. Multiple molecular mechanisms contribute to recurrence in patients following initial treatment for advanced epithelial ovarian cancer including those involving the tumor microenvironment, tumor immune status, cancer stem cells, DNA repair/cell survival pathways and extracellular matrix. Major conclusions: Due to the adaptive nature of recurrent tumors, the major contributing and specific resistance pattern may largely depend on the nature of the primary tumor itself. General significance: Future work that aims to elucidate the complex pattern of acquired resistance will be useful for predicting chemotherapy response/recurrence following primary diagnosis and to develop novel treatment strategies to improve the survival of patients with advanced epithelial ovarian cancer, especially in tumors not harbouring homologous DNA recombination repair deficiencies.
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U2 - 10.1016/j.bbagen.2018.11.005
DO - 10.1016/j.bbagen.2018.11.005
M3 - Review article
C2 - 30423357
AN - SCOPUS:85056865914
SN - 0304-4165
VL - 1863
SP - 371
EP - 378
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 2
ER -