Early detection of cancer and of treatment resistance

Anne Pradines and Julien Mazières

Our team is strongly involved in translational and clinical cancer research. Our main objective is to understand the tolerance of targeted therapies and to discover new biomarkers for the early management of patients with lung cancers in particular. The team, member of the European Liquid Biospy Society, is focused on liquid biopsies (e.g. circulating nucleic acids, circulating tumor cells (CTC)) for diagnosis, prognosis, longitudinal follow-up of the disease and prediction of the therapeutic response.

In the framework of the LUNG-RESIST project led by Pr. J. Mazières, which aims to understand and overcome adaptive resistance to EGFR tyrosine kinase inhibitors EGFR-TKi in lung cancer, a prospective clinical study has been opened in January 2021. Response to treatment and detection of minimal residual disease are assessed by analysis of circulating tumor DNA up to relapse, and CTC analysis offers the unique opportunity to characterize tolerant cells in the patient.

The team also participates in the translational project YODA led by Pr. F. Clément-Bidard (Institut Curie), whose objective is to evaluate the tolerance and efficacy of palbociclib combined with hormone therapy in patients with metastatic breast cancer, with NGS analysis of circulating tumor DNA.

In addition, the team is a member of the BOLERO consortium, which is interested in characterizing the molecular mechanisms that regulate the adaptability of resistance to BRAF inhibitors as well as in the search for biomarkers of resistance in lung tumors

The early detection of lung cancer is another of the team’s research axes, with the definition of a signature of plasma microRNAs (miRNOD project) and the development of tools for genotyping tumors on free plasma DNA but also from ultrasound-guided transbronchial puncture supernatants (KOBE project). In parallel, the team is associated with the collaborative and interdisciplinary project BIOLICAN which associates LAAS-CNRS, Institut de Recherche Pierre Fabre and IUCT, which aims at developing a new innovative technological device able to detect molecular signatures of clinical interest in the blood of cancer patients, in order to allow the early diagnosis of the disease

Key words:

  • Liquid Biopsies,
  • circulating tumor DNA,
  • circulating tumor cells,
  • lung cancer,
  • translational research

Group members:

  • Anne Casanova, Assistant Engineer
  • Estelle Clermont, Engineer
  • Florence Dalenc, MD, PhD, HDR (PU, PH)
  • Célia Delahaye, PhD, Postdoc
  • Gilles Favre, PharmD/PhD (PU, PH)
  • Nicolas Guibert, MD, PhD, HDR (PU, PH)
  • Laura Keller, PharmD, PhD (MCU, PH)

Main external collaborations:

  • Institut Curie,
  • LAAS,
  • Bolero Consortium,
  • ELBS
  • Selected publications:

J Thorac Oncol. 2021 May;16(5):807-816
Ilié M, Mazières J, Chamorey E, Heeke S, Benzaquen J, Thamphya B, Boutros B, Tiotiu A, Fayada J, Cadranel J, Poudenx M, Moro-Sibilot D, Barlesi F, Thariat J, Clément-Duchêne C, Tomasini P, Véronique Hofman V, Marquette C-H, Paul Hofman P,
STALKLUNG01 Study Consortium Investigators. Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC.

Clin Cancer Res. 2020, 26(23):6242-6253.
Ortiz-Cuaran S, Mezquita L, Swalduz A, Aldea M, Mazieres J, Leonce C, Jovelet C, Pradines A, Avillon V, Chumbi Flores WR, Lacroix L, Loriot Y, Westeel V, Ngo-Camus M, Tissot C, Raynaud C, Gervais R, Brain E, Monnet I, Giroux Leprieur E, Caramella C, Mahier-Aït Oukhatar C, Hoog-Labouret N, de Kievit F, Howarth K, Morris C, Green E, Friboulet L, Chabaud S, Guichou JF, Perol M, Besse B, Blay JY, Saintigny P, Planchard D.
Circulating Tumor DNA Genomics Reveal Potential Mechanisms of Resistance to BRAF-Targeted Therapies in Patients with BRAF-Mutant Metastatic Non-Small Cell Lung Cancer.

Lung Cancer. 2019;137:1-6.
Guibert N, Jones G, Beeler JF, Plagnol V, Morris C, Mourlanette J, Delaunay M, Keller L, Rouquette I, Favre G, Pradines A, Mazieres J.
Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer.

Acta Derm Venereol 2019; 99: 206–210
Keller, L, Guibert, N, Casanova, A, Brayer, S, Farella, M, Delaunay, M, Gilhodes, J, Martin, E, Balague, G, Favre, G, Pradines, A, Meyer, N.
Early Circulating Tumour DNA Variations Predict Tumour Response in Melanoma Patients Treated with Immunotherapy.

Lung Cancer. 2018;120: 108-112
Guibert N, Delaunay M, Lusque A, Boubekeur N, Rouquette I, Clermont E, Mourlanette J, Gouin S, Dormoy I, Favre G, Mazieres J, Pradines
A. PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab.

Ann Oncol. 2018 29(4):1049-1055.
Guibert N, Hu Y, Feeney N, Kuang Y, Plagnol V, Jones G, Howarth K, Beeler JF, Paweletz CP, Oxnard GR.
Amplicon-based next-generation sequencing of plasma cell-free DNA for detection of driver and resistance mutations in advanced non-small cell lung cancer.

Lung Cancer. 2018;122:72-75
Guibert N, Tsukada H, Hwang DH, Chambers E, Cibas ES, Bale T, Supplee J, Ulrich B, Sholl LM, Paweletz CP, Oxnard GR.
Liquid biopsy of fine-needle aspiration supernatant for lung cancer genotyping.

Oncotarget 2017; 8: 38056-38060.
Guibert N, Mazieres J, Delaunay M, Casanova A, Farella M, Keller L, Favre G, Pradines A.
Monitoring of KRAS-mutated ctDNA to discriminate pseudo-progression from true progression during anti-PD-1 treatment of lung adenocarcinoma.

Lung Cancer 2016; 100: 1-4.
Guibert N, Pradines A, Farella M, Casanova A, Gouin S, Keller L, Favre G, Mazieres J.
Monitoring KRAS mutations in circulating DNA and tumor cells using digital droplet PCR during treatment of KRAS-mutated lung adenocarcinoma.

J Thorac Oncol 2016; 11: e109-112.
Guibert N, Pradines A, Casanova A, Farella M, Keller L, Soria JC, Favre G, Mazieres J.
Detection and Monitoring of the BRAF Mutation in Circulating Tumor Cells and Circulating Tumor DNA in BRAF-Mutated Lung Adenocarcinoma.

Acta Derm Venereol 2016; 96: 29-34.
Armand-Labit V, Meyer N, Casanova A, Bonnabau H, Platzer V, Tournier E, Sansas B, Verdun S, Thouvenot B, Hilselberger B, Doncescu A, Lamant L, Lacroix-Triki M, Favre G, Pradines A.
Identification of a Circulating MicroRNA Profile as a Biomarker of Metastatic Cutaneous Melanoma.

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