Normal & pathological angiogenesis

Current lab members:

Gilles PAGÈS, Research Director, DRCE INSERM
Roser Busca: CR HC CNRS
Sonia Martial: CR HC CNRS
Philippe Lenormand: CRCN INSERM
Frédéric Luciano: CRCN INSERM
Sandy Giuliano: CRCN INSERM
Cercina Onesto: MCU UCA
Saharnaz Sarlak: Post Doc ARC
Meng Tsai: Post Doc ANR JCJC
Rima Salma: Post Doc ANR JCJC
Monsef Idrissi: engineer CNRS student in bioinformatics
Arthur Gouraud: Engineer Cancéropole
Olivia Rastoin: Engineer Roca Therapeutics
Manon Teisseire: PhD FRM
Jessy Sirera: PhD UCA
Arthur Karaulic: PhD UCA
Audrey Bennetot: Master
Clara Fialon: Master

Lab Alumni:

Our projects have focused on the ERK signaling pathway ; modulation of its activity, its role in tumor development (use of ERK1-/- mice) and its role in tumor angiogenesis (regulation of VEGF expression). We have highlighted regulators of VEGF expression that can serve as markers of tumor aggressiveness especially in the case of head and neck and breast cancers. We have established an original link between telomeric activity and the ERK signaling pathway. We are also interested in phenomena that could explain the varying efficiencies of Avastin/Bevacizumab (BVZ) depending on cancer origins. On models of breast and prostate cancers, the clinical efficiency of associations Taxol / BVZ could be explained by a direct effect on tumor cells expressing both VEGF and its receptor VEGF-R2. Clear cell renal cell carcinomas (RCC) express VEGF and pro-angiogenic factors of the family of ELR+CXCL cytokines. CXCL7 and CXCL8 (interleukin 8) are associated with increased mortality in patients. Monoclonal antibodies targeting CXCL7 and 8 are currently developed. In xenograft models of RCC tumors, BVZ accelerates tumor growth and induces the development of the lymphatic network that can explain the acceleration of the metastatic spread observed in patients.

Background of the team and self analysis

The group was created in 1999 when we moved from the Centre de Biochimie Parc Valrose to the Nice Cancer Centre, Centre Antoine Lacassagne (CAL). Our objectives were to decipher the links between activation of the ERK pathway and abnormal angiogenesis, two mains actors implicated in tumor development. Our localization at the CAL incited us to develop translational research aiming at reinforced the links with clinicians. My team was implicated in the discovery of new pertinent direct targets of ERK and on the molecular links between ERKs and regulation of VEGF expression at transcriptional and post transcriptional levels. Discussions with clinicians and our expertise on angiogenesis have oriented our thematic on the failure of anti-angiogenic therapies. The identification of the phosphorylation of the telomere binding factor TRF2 by ERK has established a new link between telomeric activity and activation of a major signaling pathway involved in tumor development.

Funded Projects

Publications

Connective tissue growth factor contributes to resistance to anti-angiogenic therapies in renal cancer
9 mars 2026 par Manon Teisseire
CONCLUSION: CTGF is a key mediator of resistance to AATs in ccRCC, by promoting tumor progression and remodeling the tumor microenvironment. CTGF may thus serve as both a predictive biomarker and a therapeutic target. These findings support further investigation of CTGF inhibition as a strategy to overcome AAT resistance and improve treatment outcomes in ccRCC patients.
Improving angiogenesis ameliorates the efficacy of ASO-based exon skipping for the treatment of Duchenne muscular dystrophy
3 février 2026 par Mathilde Blitek
Duchenne muscular dystrophy (DMD) is a severe X-linked disease caused by pathogenic variants in the DMD gene, resulting in the absence of functional dystrophin. Antisense oligonucleotide (ASO)-based therapies aim to restore the open reading frame and produce a truncated but functional dystrophin protein. Although several ASOs are approved in the United States and Japan via accelerated approval procedures, dystrophin restoration in patient biopsies remains low, underlining the need to improve ASO…
Exploring Novel Applications: Repositioning Clinically Approved Therapies for Medulloblastoma Treatment
27 novembre 2025 par Arthur Karaulic
CONCLUSIONS: Medulloblastoma displays subtype-specific expressions of FDA-approved TKI, ICI and pro-apoptotic drug targets, impacting overall survival. Clinical trials investigating these approved treatments in medulloblastoma are therefore warranted.
IF-CRIB: A 3D-printable device to facilitate immunofluorescence experiments and its application in screening and characterizing cells expressing a degradable form of ERK2
11 août 2025 par Elsa Berliocchi
Immunofluorescence-based detection of proteins in fixed cells is a powerful tool for research in cell and developmental biology. While a variety of immunofluorescence protocols exist, they can be time consuming or require expensive equipment which may not be accessible to all laboratories. A common challenge in these protocols is the numerous washing steps, particularly in experiments with numerous conditions. To address this, here we introduce the IF-CRIB device, a 3D-printable wash rack…
Comparative impact of proton versus photon irradiation on triple-negative breast cancer: Role of VEGFC in tumour aggressiveness
22 mai 2025 par Saharnaz Sarlak
No abstract
Age Does not Affect the Efficacy of Antibody Drug Conjugates, But is Associated with High-Grade Adverse Events in Patients with Cancer Enrolled in Early Phase Clinical Trials
15 mai 2025 par Ana Vaz Ferreira
CONCLUSIONS: In our cohort, ADC therapy provided comparable survival benefits for the older patients but with a higher risk of high-grade adverse event.
Enhancing radiotherapy techniques for Triple-Negative breast cancer treatment
26 avril 2025 par Saharnaz Sarlak
Breast cancer is the most prevalent cancer among women worldwide, with various subtypes that require distinct treatment approaches. Among these, Triple-Negative Breast Bancer (TNBC) is recognized as the most aggressive form, often associated with poor prognosis due to its lack of targeted therapeutic options. This review specifically focuses on Radiotherapy (RT) as a treatment modality for TNBC, evaluating recent advancements and ongoing challenges, particularly the issue of radioresistance. RT…
Aqueous humor mediator levels as biomarkers of anti-VEGF response in age-related macular degeneration
27 mars 2025 par Stéphanie Baillif
CONCLUSIONS: The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., ≤50 pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNFα levels. Treatment response correlated with high baseline VEGF-A levels. An interval > 8 weeks between the third and fourth anti-VEGF IVIs was associated with a…
De Novo Serine Synthesis Is a Metabolic Vulnerability That Can Be Exploited to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma
3 mars 2025 par Manon Teisseire
Sunitinib is an oral tyrosine kinase inhibitor used in treating advanced renal cell carcinoma (RCC) that exhibits significant efficacy but faces resistance in 30% of patients. Identifying the molecular mechanisms underlying resistance could enable the development of strategies to enhance sunitinib sensitivity. In this study, we showed that sunitinib induces a metabolic shift leading to increased serine synthesis in RCC cells. Activation of the GCN2-ATF4 stress response pathway was identified as…
Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation
30 décembre 2024 par Jessy Sirera
CONCLUSIONS: Our findings highlight the critical role of the deubiquitinase USP39, suggesting that the USP39/ZEB1 axis could serve as a potential diagnostic marker and therapeutic target in MM.
A Potent Solution for Tumor Growth and Angiogenesis Suppression via an ELR+CXCL-CXCR1/2 Pathway Inhibitor
19 juin 2024 par Oleksandr Grytsai
CXCR1/2 biomolecules play vital roles in cancer cell proliferation, tumor inflammation, and angiogenesis, making them attractive drug targets. In clear cell renal cell carcinoma (RCC) and head and neck squamous cell carcinoma (HNSCC), where CXCR1/2 is overexpressed, inhibition studies are limited. Building upon previous research efforts, we investigated new N,N'-diarylurea analogues as ELR^(+)CXCL-CXCR1/2 inhibitors. Evaluations on RCC and HNSCC cell lines and 3D spheroid cultures identified…
Unveiling CXCR2 as a promising therapeutic target in renal cell carcinoma: exploring the immunotherapeutic paradigm shift through its inhibition by RCT001
20 mars 2024 par Christopher Montemagno
CONCLUSIONS: RCT001, by inhibiting CXCR2 through its unique mechanism, effectively suppresses ccRCC cell proliferation, angiogenesis, and M2 macrophage polarization. This optimization potentiates the efficacy of immunotherapy and holds promise for significantly improving the survival prospects of metastatic ccRCC patients.
Combination of Anti-Angiogenics and Immunotherapies in Renal Cell Carcinoma Show Their Limits: Targeting Fibrosis to Break through the Glass Ceiling?
24 février 2024 par Manon Teisseire
This review explores treating metastatic clear cell renal cell carcinoma (ccRCC) through current therapeutic modalities-anti-angiogenic therapies and immunotherapies. While these approaches represent the forefront, their limitations and variable patient responses highlight the need to comprehend underlying resistance mechanisms. We specifically investigate the role of fibrosis, prevalent in chronic kidney disease, influencing tumour growth and treatment resistance. Our focus extends to…
Checkpoint inhibitors and anti-angiogenic agents: a winning combination
21 septembre 2023 par Patrick Brest
The combination of immune checkpoint inhibitors and anti-angiogenic agents is a promising new approach in cancer treatment. Immune checkpoint inhibitors block the signals that help cancer cells evade the immune system, while anti-angiogenic agents target the blood vessels that supply the tumour with nutrients and oxygen, limiting its growth. Importantly, this combination triggers synergistic effects based on molecular and cellular mechanisms, leading to better response rates and longer…
Angiogenesis and Lymphangiogenesis in Medulloblastoma Development
29 juillet 2023 par Manon Penco-Campillo
Medulloblastoma (MB) is the most prevalent brain tumor in children. Although the current cure rate stands at approximately 70%, the existing treatments that involve a combination of radio- and chemotherapy are highly detrimental to the patients' quality of life. These aggressive therapies often result in a significant reduction in the overall well-being of the patients. Moreover, the most aggressive forms of MB frequently relapse, leading to a fatal outcome in a majority of cases. However, MB is…
Should evidence of an autolysosomal de-acidification defect in Alzheimer and Parkinson diseases call for caution in prescribing chronic PPI and DMARD?
24 juillet 2023 par Sandy Giuliano
Nearly fifty million older people suffer from neurodegenerative diseases, including Alzheimer (AD) and Parkinson (PD) disease, a global burden expected to triple by 2050. Such an imminent "neurological pandemic" urges the identification of environmental risk factors that are hopefully avoided to fight the disease. In 2022, strong evidence in mouse models incriminated defective lysosomal acidification and impairment of the autophagy pathway as modifiable risk factors for dementia. To date, the…
N-terminal alanine-rich (NTAR) sequences drive precise start codon selection resulting in elevated translation of multiple proteins including ERK1/2
6 juillet 2023 par Roser Buscà
We report the discovery of N-terminal alanine-rich sequences, which we term NTARs, that act in concert with their native 5'-untranslated regions to promote selection of the proper start codon. NTARs also facilitate efficient translation initiation while limiting the production of non-functional polypeptides through leaky scanning. We first identified NTARs in the ERK1/2 kinases, which are among the most important signaling molecules in mammals. Analysis of the human proteome reveals that…
New Phenylspirodrimanes from the Sponge-Associated Fungus Stachybotrys chartarum MUT 3308
28 mars 2023 par Marie Dayras
Two phenylspirodrimanes, never isolated before, stachybotrin J (1) and new stachybocin G (epi-stachybocin A) (2), along with the already reported stachybotrin I (3), stachybotrin H (4), stachybotrylactam (5), stachybotrylactam acetate (6), 2α-acetoxystachybotrylactam acetate (7), stachybotramide (8), chartarlactam B (9), and F1839-J (10) were isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308. Their structures were established based on extensive spectrometric (HRMS) and…
A group of novel VEGF splice variants as alternative therapeutic targets in renal cell carcinoma
22 février 2023 par Christopher Montemagno
The efficacy of anti-angiogenic treatment by targeting VEGF/VEGF receptors in metastatic clear cell renal cell carcinoma (ccRCC) varies from patient to patient. Discovering the reasons behind this variability could lead to the identification of relevant therapeutic targets. Thus, we investigated the novel splice variants of VEGF that are less efficiently inhibited by anti-VEGF/VEGFR targeting than the conventional isoforms. By in silico analysis, we identified a novel splice acceptor in the last…
Targeting of the ELR+CXCL/CXCR1/2 Pathway Is a Relevant Strategy for the Treatment of Paediatric Medulloblastomas
11 décembre 2022 par Manon Penco-Campillo
Medulloblastoma (MB) is the most common and aggressive paediatric brain tumour. Although the cure rate can be as high as 70%, current treatments (surgery, radio- and chemotherapy) excessively affect the patients' quality of life. Relapses cannot be controlled by conventional or targeted treatments and are usually fatal. The strong heterogeneity of the disease (four subgroups and several subtypes) is related to innate or acquired resistance to reference treatments. Therefore, more efficient and…

Lab News

UniCA 2025 Excellence Awards evening

5 IRCAN members were honored at the UniCA 2025 Awards of Excellence Ceremony held on December 11 at the Théâtre du Château de Valrose.Congratulations to: Find all the details in
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Fête de la Science – Village des Sciences de Nice – 10, 11 et 12 octobre 2025

Cette année encore de nombreux IRCANiens se sont mobilisés pour accueillir le public et animer des ateliers permettant d’illustrer les recherches sur le cancer et le vieillissement menées à l’IRCAN.
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Roca Therapeutics secures first-ever EMA recognition of Radiation Maculopathy as distinct indication – and Orphan Drug Designation

We are proud to announce that the drug candidate RCT002, developed at IRCAN (by Gilles PAGES’ team and Maeva DUFIES) and ICN, patented with SATT Sud-Est and licensed to Roca
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Seminar Series – Canceropole PACA

Suivez le séminaire de Sandy GIULIANO, « Unintended lysosomal accumulation of anti-cancer drugs: a driver of metabolic deregulation », en visioconférence aujourd’hui, mardi 24 juin à partir de 13h dans le cadre
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La start-up Roca Therapeutics lauréate du financement européen FEDER-FSE+

La start-up Roca Therapeutics, spin-off d’Université Côte d’Azur et de la SATT Sud Est, est lauréate du financement « Programme Provence-Alpes-Côte d’Azur et Massif des Alpes FEDER-FSE+-FTJ 2021-2027 » dans le cadre
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