SENESCENCE THERAPY · "PRO –SENESCENCE” THERAPY IN PEDIATRIC BRAIN TUMORS""
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2009-02-23 → 2013-02-22
- Финансиране от ЕС
- 100 000 €
- Участници
- 2
- Схема
- MC-IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Ефективността на инхибитора VO-OHpic се тества върху детски тумори в мозъка, за да се предизвика спиране на растежа на раковите клетки. Това помага за разработването на нови методи за ограничаване на развитието на медулобластоми и невробластоми при деца.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
'Pro-senescence' therapy in pediatric brain tumours
Cellular senescence, an irreversible cell growth arrest, is an intrinsic tumour suppressor mechanism which opposes tumourigenesis in vivo. We have recently discovered a novel type of cellular senescence response that can be elicited by acute loss of the tumour suppressor phosphatase and tensin homologue (PTEN) one of the main tumours suppress genes altered in cancer. While subtle reduction of PTEN levels promote tumour initiation and progression, we have recently demonstrated that complete inactivation of PTEN drives senescence even in arrested cells in absence of hyper-replication and a deoxyribonucleic acid (DNA) damage response. We have named this novel senescence response; PTEN-loss-induced cellular senescence (PICS). Importantly, we have demonstrated that this senescence response depends on the functional activity of mammalian target of rapamycin (mTOR) mediated p53 translation. Therefore, loss of the tumour suppressor p53 promotes senescence evasion, tumour invasion and cancer progression. Importantly, we have recently demonstrated that PTEN pharmacological inhibition drives senescence and tumour growth arrest in vivo, in a prostate cancer xenograft model. Medulloblastoma (M) and neuroblastoma (N) are two main intra- and extra-cranial paediatric tumours. While these tumours are usually associated with alteration of the proto-oncogenes c- myc and n-myc, they retain a normal PTEN and p53 status. Therefore, these represent an ideal model system to test the efficacy of novel 'pro-senescence' compounds either alone or in combination. The primary aim of this Marie Curie project is to demonstrate the efficacy of the novel PTEN inhibitor, VO-OHpic, in this model system. Secondary aim of this project is to test the potential synergy between VO-OHpic and the compounds that can stabilize p53 such as the MDM-2 inhibitor, Nutlin-3, and different DNA damage agents (i.e. X-radiation). Giving the current effort in identifying novel non-cytotoxic compounds for the treatments of paediatric tumours our project has provide additional therapeutics options to the cure of these frequent paediatric tumours.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The irreversible cell growth arrest, termed cellular senescence, is emerging as an intrinsic tumour suppressive mechanism, which restricts progression of early cancerous lesions in humans. We have recently reported, a new type of cellular senescence, which occurs after the acute inactivation of the tumour suppressor Pten and significantly opposes tumorigenesis in vivo. Pten induced cellular senescence (PICS) occurs at early time points after Pten inactivation even in absence of cellular proliferation and DNA Damage. I will discuss the mechanism that trigger PICS in cancer, hailing the potential therapeutic implication of p53 stabilizing drugs and Pten inhibitors. Importantly, I will discuss how the oncogenic stress induced by complete loss of Pten can still triggers senescence in cells with low proliferative potential, such as cancer stem cells. I propose to apply this model to the treatment of pediatric brain tumors.
Оригинален текст от CORDIS (на английски).
Участници
Връзки
Данни: CORDIS, © Европейски съюз