Anti-angiogenic drug · Multifunctional Polymeric Nanomicelles Combat Tumor Evasion in Antiangiogenic Cancer Therapy
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2014-05-01 → 2018-04-30
- Финансиране от ЕС
- 100 000 €
- Участници
- 1
- Схема
- MC-CIG
Линиите свързват координатора с партньорите.
Накратко на български
Полимерни наночастици с лекарството карбеноксолон се тестват за блокиране на кръвоснабдяването на туморите и предотвратяване на метастази в белите дробове. Това помага да се преодолее устойчивостта на рака към терапията, която често се активира при умирането на туморните клетки.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Multifunctional Polymeric Nanomicelles Combat Tumor Evasion in Antiangiogenic Cancer Therapy
Formation of new blood vessel in a process called angiogenesis plays a pivotal role in tumor development and metastases.Angiogenesis supports tumor proliferation and progression, and is often associated with poor disease prognosis. Recent advances in targeting angiogenesis and inhibiting tumor neovascularization led to numerous new antiangiogenic drugs, which are now in clinical use for treating various cancers such as renal cancer, colorectal cancer and several other solid tumors. However, despite the promise, the efficacy of these treatments is relatively limited and similar to chemotherapy, these therapies also show tumor “resistance” over time, through different compensating mechanisms. Ultimately, anti-angiogenic therapy (specific or broad spectrum) aims to starve tumor tissue by damaging its blood supply. As a result of these therapies, tumor tissue becomes hypoxic and eventually necrotic. While tumor death by necrosis is considered a desirable outcome of treatment, paradoxically it also triggers another mechanism of tumor evasion, by the secretion of pro-inflammatory and pro-angiogenic signals from necrotic tissue and also due to re-vascularization. In this project we have successfully fabricated and characterized lung targeted, drug carrying PLGA polymer carriers, using Carbenoxolone, an already approved drug which was recently identified as an antagonist of the necrotic signal HMGB1. We demonstrated the anti-cancer and anti-angiogenic effects of the free drug using both in-vitro and several in-vivo models. We showed that the drug loaded particles maintain the effect of the drug in the lung, proving this treatment to be effective as a targeted prophylactic treatment for lung metastases. Moreover, after setting a novel in-vitro system of mimicking the tumor microenvironment, we conducted a proteomic analysis, and have identified several interesting necrotic signals as possible future therapeutic targets. We are now focusing on our next challenge of modifying our drug carriers to be used as a dual drug release system in vivo for improvement of treatment efficacy. The carriers will combine two drugs: a potent anti-angiogenic drug and an antagonist of a necrotic signal. Using this innovative approach we attempt to significantly improve tumor treatment by minimizing resistance to drug over time.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Angiogenesis a major contributor to tumor development and metastases. Formation of new blood vessels supports tumor proliferation and disease progression and is often associated with poor clinical prognosis. Recent advances targeting angiogenesis and inhibition of tumor neovascularization has led to the approval of several new antiangiogenic drugs for clinical use in many types of cancers. Yet despite promising potential, the efficacy of these treatments has been relatively limited. Additionally, as with chemotherapeutics, over time these therapies are associated with tumor resistance and escape. Antiangiogenic therapy (target-specific or broad spectrum) aims to eradicate the tumor by damaging its blood supply; as a result tumor tissue becomes hypoxic and, consequently, necrotic. By current clinical measure, this tissue death is considered a positive outcome; however it is recently discovered that the necrotic tissue in turn releases signals contributing to inflammation and angiogenesis, eventually initiating aggressive revascularization, overriding the foreseen beneficial effects of the antiangiogenic drug. For this grant, we propose to design a novel drug-delivery system based on multifunctional polymer nanomicelles which combine two small molecule drugs: one a potent antiangiogenic drug, and second which is an antagonist of these necrotic signals, combating the feed-back loop which can undermine the positive effects of therapy. Using this innovative approach, we intend to significantly improve cancer treatment by minimizing resistance to antiangiogenic drugs. This technology is based on our previous development of the PEG-PLA polymer conjugate of a small molecule angiostatic compound, TNP-470, which form nanomicelle with improved pharmacological properties compared with the free drug. By combining a second drug with distinct mechanism of action we will provide an important, clinically relevant tool, and a future platform for antiangiogenic or other drugs.
Оригинален текст от CORDIS (на английски).
Участници
- THE HEBREW UNIVERSITY OF JERUSALEM · JerusalemКоординаторИзраел
Връзки
Данни: CORDIS, © Европейски съюз