Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol

Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as c...

Full description

Saved in:

Bibliographic Details
Published in:	Heliyon Vol. 10; no. 1; p. e23170
Main Authors:	van der Ploeg, Phyllis, Hendrikse, Cynthia SE, Thijs, Anna MJ, Westgeest, Hans M., Smedts, Huberdina PM, Vos, M Caroline, Jalving, Mathilde, Lok, Christianne AR, Boere, Ingrid A., van Ham, Maaike APC, Ottevanger, Petronella B., Westermann, Anneke M., Mom, Constantijne H., Lalisang, Roy I., Lambrechts, Sandrina, Bekkers, Ruud LM, Piek, Jurgen MJ
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 15-01-2024 Elsevier
Subjects:	Off-label drugs Ovarian cancer Signal transduction pathways Survival targeted therapy Signal transduction pathways targeted therapy Survival Off-label drugs Ovarian cancer
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2405-8440 2405-8440
DOI:	10.1016/j.heliyon.2023.e23170