Back to search

FRIMED2-FRIPRO forskerprosjekt, medisin og helse

Defining relevant targets for personalizing gynecologic cancer treatment

Alternative title: Persontilpasset behandling ved gynekologisk kreft

Awarded: NOK 9.0 mill.

Project Manager:

Project Number:

239840

Application Type:

Project Period:

2015 - 2021

At time of metastatis gynaecological cancer need new and more targeted treatment. The study examines the effects of such new and more targeted medications. In addition we investigate promising new biomarkers that can be used to prevent over-treatment with associated side effects in patients with little risk of developing recurrence. Cancer of the uterine lining (endometrium) increases and is currently the most common gynaecological cancer, while ovarian cancer is the most lethal form of cancer of the genitals. A number of risk factors have been identified, but the cause is still largely unknown. For uterine cancer bleeding after menopause will often be an early symptom while the disease is still surgically curable. Cervical cancer is combated through an effective screening program. Ovarian cancer is however often detected late with distant spread. For all gynaecological cancers with disease spread, the likelihood of being cured is small. The lack of progress can be attributed to suboptimal testing of new drugs. In addition there are few opportunities to study the impact of such new drugs using so-called preclinical models (cell line studies / animal models) that adequately reflect women with gynaecological cancer. We have therefore chosen the following strategies to improve our knowledge: (1) We map a comprehensive landscape of genetic alterations being possible targets for the treatment of primary and metastatic tumors respectively. (2) We develop better cell/animal models to investigate promising targeted drugs for new treatment. (3) We develop better methods for advanced imaging of tumours (functional MRI, PET-CT) to follow disease progression during treatment. This may provide new tools to register response to treatment as early as possible. (4) We test if biomarkers may aid in choosing less aggressive surgical treatment for low-risk patients (avoid Lymphadenectomy). (5) We investigate systematically the quality of life of women treated for endometrial cancer to evaluate the effect of treatment modalities such as chemotherapy and whether avoiding removal of pelvic lymph nodes) will affect her quality of life during/after treatment.

Vi har fått gjennomført god oppfølgning av studiepasienter med endometriecancer. I perioden er behandlingsendring gjennomført med skifte fra rutinemessig lymfadenektomi til biomarkørselektert lymfadenektomi med et bibehold av god overlevelse. Vi har fått data på pasienters livskvalitet under/etter behandling, og sett ulik effekt mhp om det er gjort lymfadenektomi og/eller gitt cellegiftbehandling. Langtidsevaluering når hele studiekohorten har gjennomført 5-års oppfølgning vil gi ytterligere vurdering av ulike behandlingseffekter. Studien har bidradd til å videreutvikle avansert billeddiagnostikk for ytterligere risikostratifisering av svulstene. Det er etablert cellelinjer, 3D cellekulturer, musemodeller og utført avanserte genetiske studier som alle bidrar til å utvikle bedre forståelse av svulstutvikling og risikoprofil samt tilrettelegger for uttesting av nye medikamenter.

Gynecologic cancers have significant histologic, phenotypic and molecular overlap. The challenge is to translate this knowledge into improved clinical care. Our research environment has available data from patients with molecularly comprehensively characterized primary and metastatic lesions in parallel with complete clinical data and results from preoperative advanced imaging. We have already demonstrated the capacity to (1) build a team of clinical, para-clinical and basic scientists. (2) Develop long-term local, regional, national and international collaborations. (3) Generate novel research data, published in Nature, PNAS, Lancet Oncology and JCO as driving investigators. (4) Gain confidence from national and international colleagues as PI for the MoMaTEC-1 trial, including >1500 cases. (5) Include >300 patients, in parallel with molecular profiling of primary and metastatic lesions, in protocols for functional imaging (fMRI and PET-CT) and (6) Develop methods for personalized tumor grafts of metastatic gynecologic cancer. We now plan to take our previous studies to the next level to integrate biomarkers to improve patient care addressing the two major clinical challenges: 1. Overtreatment of early stage disease. 2. Poor survival and lack of targeted therapy in clinical use in metastatic disease. We propose the following approach to develop novel methods in diagnostics and improve risk stratification of patients: Perform a Phase IV study of validated biomarkers in a prospective international biomarker implementation trial for stratified surgery (MoMaTEC2) (WP1). Test for drug response in orthotopic tumor grafts with specific targetable lesions enriched in metastases (WP2). Explore functional imaging of animal models and patients in parallel related to molecular tumor subtypes (WP3). Perform a biomarker (Stathmin) integrated Phase 2B clinical trial of treatment with weekly paclitaxel potentially continued as a Phase 2B randomized biomarker integral study (WP4

Publications from Cristin

No publications found

No publications found

No publications found

No publications found

Funding scheme:

FRIMED2-FRIPRO forskerprosjekt, medisin og helse

Funding Sources