H2020Индивидуална стипендия2015–2017

ACM · Cholesterol metabolism as a driver of prostate cancer aggressiveness

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-04-01 → 2017-03-31
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Метаболизмът на холестерола и влиянието на лекарства като симвастатин върху развитието на рака на простатата се анализират чрез миша модели и данни от пациенти. Това помага да се разбере дали определени терапии могат неочаквано да ускорят болестта при конкретни групи мъже.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Cholesterol metabolism as a driver of prostate cancer aggressiveness

Metabolic syndrome, obesity, and high cholesterol levels have been shown to increase the risk of prostate cancer, one of the malignancies with the highest incidence among man in Europe. However, the data relating cholesterol and prostate cancer is yet controversial and the extent of increased risk varies among studies. This notion is in agreement with the fact that tumour cells reprogram their utilization and biosynthesis of cholesterol, which is frequently elevated in obese individuals. In order to better understand the contribution of obesity to the biology of prostate cancer, we took advantage of genetic mouse models of the disease. We hypothesized that cholesterol could be a contributing factor to the effect of obesity on prostate cancer pathogenesis. As proof-of-concept, we tested whether anti-cholesterolemic treatment would hamper prostate cancer in the context of obesity. For that we chose one the most commonly used anticholesterolemic drugs, simvastatin. Unexpectedly, simvastatin treatment did not reduce the phenotype, but instead we observed full blown prostate cancer lesions emerging. Next, we evaluated the effect of anticholesterolemic treatment in the absence of obesity and the results also indicated that simvastatin increased prostate cancer therapy resistance and accelerated its appearance. Moreover, in collaborations with clinicians, we showed that certain subgroup of patients could increase the incidence of prostate cancer when treated with statins. These results are very relevant socially because although the epidemiological studies didn’t show that statins in general increased the risk to any cancer. However, our results might be uncovering an undesired effect of this treatment on an unknown group of man. For that reason, our objectives are to keep investigating in the mechanisms of this phenomenon to clarify the possible risk of these drugs on the general population.

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

Цел на проекта

According to the WHO, prostate cancer (PCa) is the most common cancer in men in the European Union (EU). The currentview of cellular transformation and cancer progression supports the notion that cancer cells must undergo a metabolicreprogramming in order to survive in a hostile environment. Tumors are not homogeneous entities, and most cancers retaina differential fraction of cells with increased self-renewal capability (cancer stem or initiating cells), that accounts forrecurrence and resistance to therapy. While we know more about the metabolism of tumor cells and its implication in cancer,our knowledge about the metabolism of cancer-initiating cells remains insufficient.Obesity is associated with increased risk of prostate cancer metastasis and death. On other side, statins treatment reducesthe risk of PCa, indicating that cholesterol might have a role in the onset of the disease. Overweight and obesity rates in EUaffect 50 and 20% of the population respectively. Therefore, it is critical to define the role of environmental factors such asnutrition and “lifestyle” for cancer prevention.Preliminary studies in our lab indicate that cancer initiating cells are highly enriched in cholesterol synthesis genes and theirsphere formation capacity is dependent on cholesterol synthesis. We hypothesize that an active cholesterol metabolism isessential for prostate cancer-initiating cell function, and that the use of cholesterol synthesis inhibitors might target this subpopulation of aggressive cancer cells.I will use a combined transcriptomic and metabolomic approach to define the alterations of cholesterol metabolism. I willstudy the mechanisms by which cholesterol metabolism regulates CIC function. I will study the feasibility of therapeutictargeting of cholesterol metabolism in prostate cancer using a well established mouse model. And finally, I will do aprospective associative study of statin treatment with CICs markers expression in patients.

Оригинален текст от CORDIS (на английски).

Участници

ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS · DERIO VIZCAYAКоординаторИспания