Project: TREatment DEcision baSed on organoIds in Gastric caNcer

Acronym	REDESIGN (Reference Number: ERAPERMED2021-302)
Project Topic	The era of precision oncology utilises novel approaches to tailor treatment to improve outcomes to the benefit of the patient. Today cancers can be molecularly dissected, and patients with targetable mutations can be stratified to receive tailored therapies. However, most therapies often cause a short-lived response, as patients that initially respond will develop resistance after a period of disease control. Two different mechanisms are important in the aetiology of resistance: firstly, intratumoral heterogeneity, the presence of pre-existing resistant tumour subclones. Secondly, accumulating mutations that circumvent the point of action of a given drug. Deciphering intratumoral heterogeneity is key to developing combinatorial drug strategies that account for a priori resistant subclones. Predicting mutations that emerge under selective pressure of treatment will enable early identification of upcoming drug resistance, allowing tailored treatment strategies before the patient actually becomes resistant. The REDESIGN consortium proposes a multidisciplinary programme based on patient-derived organoids (PDOs) to guide personalised treatment in gastric cancer patients. By integrating functional drug response data from PDOs from pre-and post-treatment specimens, dissecting clonal evolution and mutational adaptation of PDOs under selective treatment pressure, as well as CRISPR/Cas9 engineered human organoids, the consortium aims to unravel treatment resistance mechanisms and design treatment strategies that consider the identified causes of resistance. Further, the patient's point of view will be taken into account in personalised treatment decisions. The overarching aim is to improve personalised treatment by combining the gained knowledge of evolutionary trajectories and mechanisms of resistance to therapy as well as addressing ethical and social challenges when using PDOs to aid clinical decision making in the era of precision medicine.
Network	ERA PerMed
Call	4th Joint Transnational Call for Proposals (2021)

Project partner

Number	Name	Role	Country
1	TU Dresden	Coordinator	Germany
2	University of Copenhagen	Partner	Denmark
3	Institute of Molecular Biotechnology of Austrian Academy of Sciences (IMBA)	Partner	Austria
4	Max Planck Institute for the Physics of Complex Systems	Partner	Germany