les cellules

Projet 5 – Quattour : an effective drug combination to combat cancer

Auteurs

Nowak-Sliwinska Patrycja, School of Pharmaceutical Sciences and Institute of Pharmaceutical Sciences of Western Switzerland, UNIGE Patrick Meraldi, Département de Physiologie Cellulaire et Metabolisme, Faculté de Médecine, UNIGE

Résumé du projet

Cell division is an attractive target for anti-cancer treatments, but patients treated with classical cell division drugs develop resistance due to high doses and suffer from severe side effects due to impaired divisions of healthy cells. We have discovered a promising mixture of four low-dose (QUATTOUR) drugs that kill dividing tissue cells from diverse cancer types while leaving healthy cells undamaged. A key next step is to test the efficacy and security of QUATTOUR in an animal setting.

Introduction

Anti-cancer drugs should target cancer cells features that are absent in healthy cells. Excessive centrosome number are frequent in cancer cells and can lead to lethal multipolar cell divisions. Cancer cells possess a survival mechanism absent in healthy cells, called centrosome clustering that suppresses multipolar spindles. Genetic proof-ofprinciple experiments proved that blocking centrosome clustering effectively kills cancer cells, but corresponding drug treatments are still missing.

Innovation

We have discovered a synergistic combination of four low-dose (QUATTOUR) drugs that blocks centrosome clustering in cancer cells while leaving healthy cells unaffected. QUATTOUR is composed of low doses of the established anti-cancer drugs tubacin, CI-994, erlotinib and dasatinib. Such low-dose synergistic combinations target cancer cells from several angles, preventing resistance acquisition, and eliciting milder side-effects, as the individual drugs are used well below the maximally tolerated concentrations. QUATTOUR kills cancer cells with excessive centrosome numbers from many cancer types, indicating that it acts independently of the organ of origin. None of the drugs composing the mixture prevents centrosome clustering when applied alone, highlighting its synergistic effect. QUATTOUR is based on over 4 years of collaborative research between the Medical Faculty and the Pharmacy section of the UNIGE. A patent has been filed to protect QUATTOUR (EP19199136).

Avantages

QUATTOUR is a selective and safe drug mixture that has the potential to solve a significant unmet medical need for cancer patients. The envisioned drug mixture will have a significant benefit for improving patient compliance, risks and finally treatment costs.

Advantages: + Save to the patient + Simplified life-long treatment: chronic dosing for optimal outcomes.

+ Easily accessible “anywhere, any time” (self-administered daily oral treatment, with no injection requirement) + QUATTOUR doses can be adjusted in the personalized fashion at any time of the treatment course + Simple and rapid protocol of preparation + Non-organ related: cancers presenting a high percentage of cells prone undergo multipolar division

Résultats préliminaires

We demonstrated in various in vitro tissue culture models that QUATTOUR effectively impairs centrosome clustering and the division multiple cancer types, and that it preferentially targets cancer cells bearing centrosome abnormalities. Importantly, in all tested cells types, QUATTOUR did not affect the survival or the division of corresponding healthy cells. The effect on cancer cells results from the synergy of the QUATTOUR combination, as none of the four monotherapies affected pole clustering on their own at the tested dose range.

Développements

- Incising the spectrum of cancer types possibly treated with the QUATTOUR - Testing QUATTOUR activity in multiple cancer types in complex in vitro models: 3D heterotypic co-cultures

Conclusion (si vous remportez un prix, comment l'utiliserez-vous pour faire avancer votre projet ?)

The prize would enable testing QUATTOUR in vivo studies confirming its efficacy and safety. The acquired data would de-risk the product development and would attract prospective commercial partners for co-development.