Welcome to the ESMO Gynaecological Cancers Congress 2022 Welcome and closure

Welcome to the ESMO Gynaecological Cancers Congress 2022

Lecture Time
08:30 - 08:35
Speakers
  • The Panelists (Valencia, Spain)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:25 - 08:30
Management of endometrial cancer in the molecular era Educational session

Live Q&A

Lecture Time
09:50 - 10:00
Speakers
  • Carien L. Creutzberg (Leiden, Netherlands)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:30 - 10:00
Management of endometrial cancer in the molecular era Educational session

Recent developments in adjuvant treatment

Lecture Time
09:00 - 09:25
Speakers
  • Carien L. Creutzberg (Leiden, Netherlands)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:30 - 10:00
Management of endometrial cancer in the molecular era Educational session

Introduction

Lecture Time
08:30 - 08:35
Speakers
  • Mansoor Raza Mirza (Copenhagen, Denmark)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:30 - 10:00
Management of endometrial cancer in the molecular era Educational session

New treatment options for advanced and metastatic disease

Lecture Time
09:25 - 09:50
Speakers
  • Alexandra Leary (Villejuif, France)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:30 - 10:00
Management of endometrial cancer in the molecular era Educational session

Recent developments in surgery for early-stage disease

Lecture Time
08:35 - 09:00
Speakers
  • Christian Marth (Innsbruck, Austria)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:30 - 10:00
Biomarkers in clinical practice and future perspective for gynaecological cancers Special session

Live Q&A

Lecture Time
11:50 - 12:00
Speakers
  • Bradley J. Monk (Phoenix, AZ, United States of America)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
10:30 - 12:00
Biomarkers in clinical practice and future perspective for gynaecological cancers Special session

Digging into molecular characterization of high-grade ovarian cancer: BRCA, HRD and beyond

Lecture Time
11:10 - 11:30
Speakers
  • Nicole Concin (Innsbruck, Austria)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
10:30 - 12:00
Biomarkers in clinical practice and future perspective for gynaecological cancers Special session

Should we really use PD-L1 as a selection driver in cervical cancer?

Lecture Time
10:30 - 10:50
Speakers
  • Bradley J. Monk (Phoenix, AZ, United States of America)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
10:30 - 12:00
Biomarkers in clinical practice and future perspective for gynaecological cancers Special session

The role of MAPK pathway to select therapy in low-grade ovarian cancer

Lecture Time
11:30 - 11:50
Speakers
  • Susana Banerjee (London, United Kingdom)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
10:30 - 12:00
Biomarkers in clinical practice and future perspective for gynaecological cancers Special session

MMR status, TMB or both: How to identify endometrial cancer patients who benefit the most from immunotherapy

Lecture Time
10:50 - 11:10
Speakers
  • Vicky Makker (New York City, NY, United States of America)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
10:30 - 12:00
Poster Display session Poster Display session

1P - Comprehensive assessment of gene mutations revealed overlapping responses for PARPi and chemotherapy in ovarian cancer cells

Presentation Number
1P
Lecture Time
12:20 - 12:25
Speakers
  • Alessandra Tozzi (Basel, Switzerland)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

PARP inhibitors (PARPi) have revolutionized the therapeutic landscape of epithelial ovarian cancer (EOC) treatment, showing outstanding benefits in regards to progression-free survival, especially in patients carrying BRCA1/2 mutations or harboring defects in homologous recombination repair. Yet, it remains uncertain which PARPi to choose and how to select responders by using clinical and molecular characteristics, especially in forefront therapy when platinum sensitivity is unknown.

Methods

Through a systematic literature review and the exploration of publicly available CRISPR-Cas9 library screens and Genomics of Drug Sensitivity in Cancer data, we identified potential genes linked with PARPi response. Using a CRISPR-Cas9 mutagenesis assay, we functionally tested 33 genes for PARPi and carboplatin response in six ovarian cancer (OC) cells lines.

Results

ATM was the only tested gene which induced olaparib sensitivity in a cell line-independent manner. Acquired olaparib sensitivity was also observed upon Cas9-mediated loss of MUS81, NBN, RAD51/B/C, RNASEH2A, PALB2, XRCC1, and XRCC3 in at least 3 out of 6 cell lines. As the major survival benefit of PARPi treatment was reported in chemo-sensitive tumors, we next assessed the effect of top candidate genes on olaparib, niraparib, talazoparib, and carboplatin response. Interestingly, we observed identical effects in a gene- and drug compound-independent manner on acquired drug sensitivity, supporting the strong correlation of cancer cell response to PARPi and chemotherapy. In contrast, we identified CDK12 as an essential gene for cell proliferation/survival in ovarian cancer cells, independent of PARPi and chemotherapy treatment.

Conclusions

Our data suggest a general mechanism of response to PARPi and chemotherapy as demonstrated by various overlapping gene dependencies. The screen of the genetic status of the genes identified correlated with PARPi sensitivity may allow better stratification of patients with increased benefit to this treatment.

Legal entity responsible for the study

The authors.

Funding

Swiss National Science Foundation (CRSII5_171037), Griesbach-Hallenstein Foundation (Walter Edwin Griesbach Award and Olga Hallenstein Award), Department of Biomedicine, University Hospital Basel and University of Basel.

Disclosure

All authors have declared no conflicts of interest.

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