H2020Индивидуална стипендия2020–2023

NOSCAR · decipheriNg Oncogenic SIgnalling patterns to break CAncer drug Resistance

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

Период: 2020-09-01 → 2023-08-31
Финансиране от ЕС: 304 724 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите на рака на гърдата с мутация PIK3CA се анализират, за да се разбере как раковите клетки комуникират и стават устойчиви на лекарства. Това помага за разработването на по-ефективни и по-малко токсични терапии за пациентите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

decipheriNg Oncogenic SIgnalling patterns to break CAncer drug Resistance

Breast cancer is the leading cancer in women by incidence and the second cause of cancer-related death in the female population. To cure the more advanced and aggressive cases of breast cancer, modern, targeted therapies have been proposed. However, cancer drug resistance limits the premise of targeted therapy. The project “Deciphering oncogenic signalling patterns to break cancer drug resistance” - NOSCAR - aimed to better understand how a specific type of breast cancer develops resistance to targeted therapies. The project asked how specific oncogenic mutations – the molecular causes of cancer – reprogramme information flow in the epithelial tissue, how mutation-reprogrammed tissue responds to standard drug treatments, how cancer cells interact with one another to escape these treatments and develop resistance, and how such interaction can be prevented to break cancer resistance to targeted therapy? Drug resistance in cancer is an unsolved problem in oncology and new therapy options are urgently needed to meet patient’s needs. In alignment with the EU’s Cancer Mission, NOSCAR addressed tissue-scale mechanisms of PIK3CA-mutated cancer resistance to therapies. It is expected that the study findings will prompt the development of more effective, less resistance-prone, and less toxic breast cancer treatments, and possibly, other types of epithelial cancers carrying PIK3CA mutations. This would largely benefit the societal needs – cancer patients and their families – to cure cancer or improve patient condition and quality of life with the disease. This Marie Skłodowska Curie Action (MSCA) aimed to define oncogenic cellular communication at the single cell resolution and delineate the mechanisms, which enable development of cancer resistance to targeted therapies. The 3 key objectives of NOSCAR were (1) to identify how a panel of clinically-relevant cancer causing mutations reprogramme cellular communication in a breast epithelium; (2) to define how a drug compendium targeting tumour affects information flow / cancer cell communication and what are potential escape mechanisms that cancer cells use to resist the treatment; and finally, to (3) test the findings of objective 2 and 3 in patient-derived organoids (PDOs) – miniature three-dimensional models of organs grown in a laboratory from a small sample of a patient's tissue.

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

Цел на проекта

Despite significant progress in drug therapies for breast cancer, about one fourth of patients still do not survive the disease. Modern, targeted therapies have been proposed to cure the more advanced and aggressive cases of breast cancer. However, non-genetic and genetic mechanisms of drug resistance currently limit the promise of targeted therapy. NOSCAR aims to define the oncogenic Ras/Erk and PI3K/Akt signalling states relevant to breast cancer oncogenic mutations, and delineate the mechanisms which enable development of cancer resistance to targeted therapies.NOSCAR’s objectives are: Using a quantitative cell biology framework that combines a multiplexed biosensor system that reports on Erk/Akt dynamics at single cell level, computer vision, and statistical modelling, I will:(1) produce an atlas of single-cell Erk/Akt dynamic signalling patterns that are associated with a compendium of clinically-relevant breast cancer mutations;(2) measure the signalling states in cells perturbed with clinically-relevant drugs that target different components of the Ras/Erk and PI3K/Akt pathways to evaluate how the oncogenic signalling network is rewired by drug treatment;(3) measure signalling dynamics in 3D spheroid cultures and patient-derived organoids to explore how a self-organizing cellular ecosystem can spatially control signalling at the single cell level to locally control fate decisions, and how the latter process is compromised by an oncogenic mutation.This will provide new insights about tumor heterogeneity and signaling network structures that confer robustness against drug perturbations. We expect to identify vulnerabilities that might be efficiently targeted by drug combinations, providing new avenues to treat breast cancer.The planned research together with training and mentoring that I will receive thanks to the fellowship, will enable to successfully restart my career in research and will significantly benefit my further academic career prospects.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAET BERN · BernКоординаторШвейцария