H2020Индивидуална стипендия2020–2024

IMaP · Imaging tumor vessels as a marker for p53 mutation status in cancer

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

Период: 2020-08-01 → 2024-04-20
Финансиране от ЕС: 203 852 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Връзката между мутациите в протеина p53 и структурата на кръвоносните съдове в туморите се анализира чрез специализирани изображения. Това помага за по-доброто определяне на подходящата терапия за всеки пациент според състоянието на неговия рак.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Imaging tumor vessels as a marker for p53 mutation status in cancer

As the “guardian of the genome”, the p53 protein helps control cell growth and repair DNA. However, the protein is mutated in over 50% of all cancers. When a p53 mutation occurs, its ability to control cell growth and repair DNA is impaired, allowing cancer cells to grow unchecked. These mutations are also problematic, as they are associated with increased tumor aggressiveness and resistance to conventional cancer treatments. Tailoring cancer treatment based on p53 mutation status is therefore of great interest, as it has the potential to improve treatment responses and outcomes for patients. Drugs that specifically target and restore the normal function of p53, or counteract the effects of a p53 mutation, are a new type of therapy that can be used to treat cancer based on p53 mutation status. While these p53-targeted treatments hold great promise for personalised treatment based on p53 mutation status, their use is complicated by the fact that p53 mutations can have diverse functional effects on cancer therapy. There is a need to assess the functional impact of p53 mutation status, but this has been challenging due to the lack of surrogate markers linking mutation status to functional outcomes. Given that p53 can regulate blood vessel growth and that vessel imaging is used clinically to monitor functional response to therapy, we hypothesized that blood vessel features could be a marker that would assess the functional impact of p53 mutation status. This MSCA project therefore aimed to evaluate the links between p53 mutations and various blood vessel features using advanced vessel imaging techniques and p53 response detection methods (Figure 1).

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

Цел на проекта

The p53 protein is mutated in over 50% of cancers. Because its expression often promotes tumor growth and is associated with resistance to treatment, there has been great interest in treating cancers based on p53 mutation status. However, the use of p53- targeted therapies requires knowing the mutation status. DNA sequencing is one approach, but requires invasive biopsies, and newer sequencing techniques still face technical hurdles. Non-invasive imaging techniques offer an alternative approach for detecting mutation status. Given that p53 regulates blood vessel growth, and that vessel imaging is used clinically to monitor response to cancer therapy, I hypothesize that tumor vessels could be used as an imaging marker to identify p53 mutation status. To test this hypothesis, I will measure relationships between p53 mutations and vessel structure/function using my expertise in 3D cell biology, vessel imaging, and image analysis and the unique expertise of the host lab in p53 biology, proteomics, and flow cytometry. The objectives of this interdisciplinary work are: 1) to screen the effect of p53 mutants on vessel structure in vitro; 2) to characterize the molecular response of endothelial cells to p53-targeted therapies; and 3) to image the structure and function of vessels in mutant p53 tumors in vivo. If a relationship is found between p53 mutation status and tumor vessel features, then it could lead to the development of the first imaging marker of p53 mutation status. This marker could help clinicians select p53-directed therapies to personalize therapy for each cancer patient. Apart from scientific impact, the proposed work will also expand my career prospects and scientific network in Europe. Under the mentorship of the host lab supervisor Prof. Sir David Lane, who discovered p53, I will receive focused training to strengthen and diversify the scientific and transferable skills I need to transition from postdoctoral scientist to junior group leader.

Оригинален текст от CORDIS (на английски).

Участници

KAROLINSKA INSTITUTET · STOCKHOLMКоординаторШвеция