HEИндивидуална стипендия2022–2024

OVADEX · Defining the role of the tumor microenvironment in treatment resistance of OVArian cancer through patient-Derived EXplants (OVADEX)

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 175 920 €
Участници: 2
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Средата около туморните клетки при рак на яйчниците и обменът на серин между тях се анализират чрез тъкани от пациенти. Това помага да се разбере защо някои терапии не действат и как метаболитните промени влияят на устойчивостта към лечението.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Defining the role of the tumor microenvironment in treatment resistance of OVArian cancer through patient-Derived EXplants (OVADEX)

Treatment resistance in ovarian cancer (OC) is common. Recently, new treatment approaches with the potential to improve OC management have been identified, but their therapeutic efficacy is limited due to treatment resistance. In this regard, the tumor microenvironment (TME) is emerging as a key contributor to treatment resistance, being the metabolic crosstalk between TME and OC one of the recently proposed mechanisms of contribution. Evidence shows that platinum-resistant OC cells have defects in serine biosynthesis, leading to an enhanced serine uptake (Nat Commun 2022;13(1):4578). Importantly, exogenous serine is also required for some TME components, suggesting a possible competition that could affect their anti-cancer function. Unfortunately, the lack of knowledge on the exact functional role of TME in treatment resistance in OC is mostly because current preclinical models of OC do not fully recapitulate the TME. In this context, OVADEX established four scientific objectives: • To generate patient-derived explants (PDEs) from 50 treatment naïve OC patients and evaluate their response to different treatments, including standard chemotherapy and emerging therapies. • To define metabolic changes, especially in serine biosynthesis, in the tumor before and after treatment. • To define cellular and phenotypic changes in TME components before and after treatment. • To associate changes in TME and OC cells to serine metabolism and treatment resistance.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Treatment resistance in ovarian cancer (OC) is common. Recent efforts have identified new treatment approaches with potential to improve its management, but their therapeutic effects are limited due to treatment resistances.Tumor microenvironment (TME) is emerging as a key contributor to treatment resistance, being the metabolic cross-talk between TME and OC one of the recently proposed mechanisms. The hosting lab has evidence that platinum-resistant OC cells have defects in serine biosynthesis which leads to an enhance uptake of serine. Importantly, exogenous serine is also required for some TME components, suggesting a possible competition for it and affecting their anti-cancer function. Thus, my working hypothesis is that metabolic cross-talk between TME and OC could involve serine metabolism, which could mediate treatment resistance. Unfortunately, there is a lack of preclinical models of OC that recapitulate TME to study its role. In this regard, the secondment lab developed a new ex vivo platform based on patient-derived explants (PDEs) that allows the study of TME interactions with cancer cells. In OVADEX, I will use PDEs to dissect the role of TME components in treatment response in OC, and particularly, in the metabolic reprogramming of cancer cells. My objectives are to generate OC PDEs and expose them to standard and emerging therapies, to define metabolic changes in OC cells and cellular and phenotypic changes in TME before and after treatment and to associate changes in TME and OC cells to serine metabolism and treatment resistance. To this end, I will integrate innovative techniques and the access of the hosting team to a unique registry of OC patients.Through this work, I aim to broaden my scientific expertise and my international network for pursuing an academic career in Europe. OVADEX will contribute to actualize many objectives outlined in my career development plan to become a PI in the field of preclinical models for cancer applications.

Оригинален текст от CORDIS (на английски).

Участници

KATHOLIEKE UNIVERSITEIT LEUVEN · LeuvenКоординаторБелгия
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS · AmsterdamНидерландия