9h à 9h15 (EDT) Mot d’ouverture par Michel Bouvier (Directeur général, IRIC)

9h15 à 10h (EDT) Conférence 1, Martine J. Smit

10h à 10h45 (EDT) Conférence 2, Xavier Leroy

11h à 11h45 (EDT) Conférence 3, Sébastien Carréno

11h45 à 12h30 (EDT) Conférence 4, J. Silvio Gutkind

*Chaque conférence sera suivie d’une période de questions de 15 minutes

12h30 à 12h45 (EDT) Mot de clôture par Michel Bouvier (Directeur général, IRIC)

12h45 à 13h15 (EDT) Session d’échanges avec les conférenciers

Salle 1 : Martine J. Smit (conférencière) – Shane Wright (modérateur)

Salle 2 : Sébastien Carréno (conférencier) – Maria Majellaro (modératice)

Salle 3 : Xavier Leroy (conférencier) – Guilhem Dugast (modérateur)

Salle 4 : Silvio Gutkind (conférencier) – Alexander Hauser (modérateur)

9h15 à 10h (EDT)

Conférencière : Martine J. Smit

Professeure, Biochimie des systèmes et cibles

Faculté de Science, Vrije Universiteit Amsterdam

Biographie (disponible en anglais seulement)

Résumé (disponible en anglais seulement)

Chemokine receptors play a key role in the immune system, directing leukocytes to lymphoid tissues and sites of inflammation. In addition, chemokines and their receptors are involved in organogenesis and angiogenesis, as well as in tumorigenesis.

Herpes viruses have hijacked the chemokine receptor system through expression of viral G protein-coupled receptors (GPCRs), altering cellular signaling after viral infection.

We have shown that several viral GPCRs, including the CMV-encoded chemokine receptors, signal in a constitutive manner, rewire proliferative and pro-inflammatory signaling pathways.

Interestingly, expression of these receptors has been detected in tumor samples of glioblastoma patients and its expression induced tumor formation in orthotopic xenograft model systems.

Nanobodies, single domain antibody fragments, targeting these human and viral chemokine receptors were shown to effectively attenuate proliferative signaling in vitro and tumor progression in vivo.

Formatted (monovalent/multivalent constructs) nanobodies, incorporating different modalities (fluorophores, photosensitizers, effector function) serve as important pharmacological tools to target and dissect the role of (viral) chemokine receptors in cancer.

10h à 10h45 (EDT)

Conférencier : Xavier Leroy

CSO, Domain Therapeutics

Biographie (disponible en anglais seulement)

Résumé

À venir

11h à 11h45 (EDT)

Conférencier : Sébastien Carréno

Chercheur principal, Unité de recherche sur les mécanismes de la morphogénèse cellulaire au cours de la mitose et de la migration, IRIC

Biographie (disponible en anglais seulement)

Résumé (disponible en anglais seulement)

Metastasis is responsible for 90% of cancer deaths. Metastatic cells acquire the ability to invade the surrounding stroma, to modulate the microenvironment and colonize distant organs by undergoing genetic modifications. But to acquire metastatic abilities, tumor cells also engage in a complex crosstalk with cells of the stroma.

The physiology of metastatic cells is still poorly understood, for instance, the mechanisms that prompt cancer cells to disseminate are still a mystery.

In collaboration with Michel Bouvier’s laboratory, we discovered a novel signalling pathway that can contribute to metastatic progression.

We found that the Thromboxane A2 receptor (TBXA2R) – a G-protein coupled receptor (GPCR) – activates Ezrin, Radixin and Moesin (ERMs), a family of proteins playing important roles in metastasis.

ERMs regulate cell morphogenesis by linking actin filaments and microtubules to the plasma membrane. Importantly, ERMs participate in the aggressiveness of numerous cancers by promoting cell invasion and metastasis. We developed biosensors that can individually monitor Ezrin, Radixin and Moesin activation in living cells. Using these, we identified the signalling pathway that TBXA2R engages to promote cell motility through activation of ERMs in a model of triple negative breast cancer.

11h45 à 12h30 (EDT)

Conférencier : J. Silvio Gutkind

Professeur distingué et Directeur, Département de pharmacologie, Faculté de médecine, et Directeur associé (sciences fondamentales), Moores Cancer Center de l’University de Californie San Diego (UCSD), La Jolla, Californie, États-Unis

Membre, Académie nationale de médecine

Biographie (disponible en anglais seulement)

Résumé (disponible en anglais seulement)

GPCRs are widely dysregulated in cancer, and yet largely underexploited in oncology.

GPCRs and G proteins are mutated in >25% of human neoplastic diseases, and aberrantly expressed in multiple human malignancies. Some of the most prevalent cancers deploy GPCR oncocrine networks to promote tumor growth, metastasize, and evade immunosurveillance.

In turn, targeting GPCRs and their regulated signaling circuitry can be exploited for the development of novel precision cancer treatments and to increase the response to immunotherapies.

Specifically, we will focus on uveal melanoma (UM) – the second most common melanoma subtype – which is caused by GNAQ oncogenes encoding constitutively active mutants of Gαq and Gα11 G protein α subunits.

The use of a computational platform to identify synthetic lethal gene interactions with GNAQ revealed that the tyrosine kinase FAK is a druggable target in UM. By the use of unbiased genetic screens, we recently uncovered that horizontal inhibition of FAK and the adaptive activation of ERK results in rapid regression of UM liver metastatic lesions. This finding provided the foundation for the first signal transduction-based multimodal precision therapy in metastatic UM.

Computational approaches to investigate how GPCRs modulation can be exploited to increase the response to immunotherapies will be also discussed.

Merci au commanditaire de l’événement, Domain Therapeutics