Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review

Mudra Binju, Monica Amaya Padilla, Terence Singomat, Pritinder Kaur, Yohan Suryo Rahmanto, Paul Cohen, Yu Yu

Research output: Contribution to journalArticle

Abstract

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 resistant 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.
GENERAL SIGNIFICANCE:
HGSOC is the leading cause of gynaecological cancer-related death. Recurrence following initial treatment is common. It is estimated that 85% of patients who achieve complete remission following first-line therapy for the advanced disease will relapse [79]. Thus, tumor recurrence accounts for the disease-related mortality. We highlighted recent studies and mechanisms to explain platinum-sensitive and platinum-resistant HGSOC recurrences. These molecular alterations that underpin EOC recurrence are crucial steps to develop new prognostic markers and targeted treatments to improve outcomes for patients.
LanguageEnglish
Pages371-378
JournalBiochimica et Biophysica Acta (BBA): General Subjects
Volume1863
Issue number2
DOIs
Publication statusPublished - Feb 2019

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Platinum
Ovarian Neoplasms
Tumors
Recurrence
Chemotherapy
Neoplasms
Drug Therapy
Repair
Therapeutics
DNA Repair-Deficiency Disorders
Living Wills
DNA
Tumor Microenvironment
Survival
Neoplastic Stem Cells
Stem cells
Homologous Recombination
Surgery
DNA Repair
Disease-Free Survival

Cite this

Binju, Mudra ; Padilla, Monica Amaya ; Singomat, Terence ; Kaur, Pritinder ; Rahmanto, Yohan Suryo ; Cohen, Paul ; Yu, Yu. / Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review. In: Biochimica et Biophysica Acta (BBA): General Subjects. 2019 ; Vol. 1863, No. 2. pp. 371-378.
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abstract = "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 resistant 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.GENERAL SIGNIFICANCE:HGSOC is the leading cause of gynaecological cancer-related death. Recurrence following initial treatment is common. It is estimated that 85{\%} of patients who achieve complete remission following first-line therapy for the advanced disease will relapse [79]. Thus, tumor recurrence accounts for the disease-related mortality. We highlighted recent studies and mechanisms to explain platinum-sensitive and platinum-resistant HGSOC recurrences. These molecular alterations that underpin EOC recurrence are crucial steps to develop new prognostic markers and targeted treatments to improve outcomes for patients.",
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Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review. / Binju, Mudra; Padilla, Monica Amaya; Singomat, Terence ; Kaur, Pritinder ; Rahmanto, Yohan Suryo; Cohen, Paul; Yu, Yu.

In: Biochimica et Biophysica Acta (BBA): General Subjects, Vol. 1863, No. 2, 02.2019, p. 371-378.

Research output: Contribution to journalArticle

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T1 - Mechanisms underlying acquired platinum resistance in high grade serous ovarian cancer - a mini review

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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 resistant 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.GENERAL SIGNIFICANCE:HGSOC is the leading cause of gynaecological cancer-related death. Recurrence following initial treatment is common. It is estimated that 85% of patients who achieve complete remission following first-line therapy for the advanced disease will relapse [79]. Thus, tumor recurrence accounts for the disease-related mortality. We highlighted recent studies and mechanisms to explain platinum-sensitive and platinum-resistant HGSOC recurrences. These molecular alterations that underpin EOC recurrence are crucial steps to develop new prognostic markers and targeted treatments to improve outcomes for patients.

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 resistant 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.GENERAL SIGNIFICANCE:HGSOC is the leading cause of gynaecological cancer-related death. Recurrence following initial treatment is common. It is estimated that 85% of patients who achieve complete remission following first-line therapy for the advanced disease will relapse [79]. Thus, tumor recurrence accounts for the disease-related mortality. We highlighted recent studies and mechanisms to explain platinum-sensitive and platinum-resistant HGSOC recurrences. These molecular alterations that underpin EOC recurrence are crucial steps to develop new prognostic markers and targeted treatments to improve outcomes for patients.

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