While many cellular mechanisms leading to chemotherapy resistance have been identified, there is a growing awareness that mechanical properties of tumours, such as their ability to deform, could contribute to the inefficiency of treatments.
Here, when we talk about the physical properties of tumours, we’re talking about compression. Tumours grow rapidly in a constrained volume, which results in a kind of compaction of tumour cells.
We found that compression of 3-dimensional tumor avatar causes a decrease in the effectiveness of the drug. Through mathematical theoretical modelling, we predicted and experimentally validated that this decrease in drug efficacy was due to a decrease in proliferation. Because chemotherapy targets proliferating cells, they do not die on treatment.
Our work highlights a new form of resistance to chemotherapy that is particularly relevant to pancreatic cancer tumours.
In the future this work could :
- Image solid stress in tumours to be able to predict the therapeutic response of tumours based on these parameters.
- Continue to understand how compression influences the development and treatment of pancreatic cancer.
Discover the published article :
Mechanical Control of Cell Proliferation Increases Resistance to Chemotherapeutic Agents
Ilaria Francesca Rizzuti, Pietro Mascheroni, Silvia Arcucci, Zacchari Ben-Mériem, Audrey Prunet, Catherine Barentin, Charlotte Rivière, Hélène Delanoë-Ayari, Haralampos Hatzikirou, Julie Guillermet-Guibert, and Morgan Delarue
Phys. Rev. Lett. 125, 128103 – Published 18 September 2020
Key words :
- Mechanical
- compression
- signaling
- proliferation
- chemotherapy resistance
- mathematical modeling
Contact :
Julie Guillermet- Guibert
team 17 : SigDYN – PI3K isoforms, signalling and cancerogenesis
Mail : julie.guillermet@inserm.fr and mdelarue@laas.fr
Collaborations et funders :
Morgan Delarue (LAAS-CNRS) and Julie Guillermet-Guibert (Inserm) are co-corresponding authors of this study. This project is part of the cross-cutting program called Oncodevice that led the CRCT to develop a close partnership with LAAS.
Program funded by the local foundation Toulouse Cancer Health, the GSO and the Cancer Plan.
One picture :
Avatar photos of tumors in 3D culture in liquid (top) or under pressure (bottom). Photos: Silvia Arcucci/ Dani Najar
