Program 1

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Inside-cell abnormality study

Embryonic pathways in tumor cells- role in progression and resistance

Understanding the “resistance phenomenon” is a major challenge in the development of new therapies against cancer. This resistance may have stemed from checkpoint proteins mutations or embryonic pathway activation; its characterization is critical to enhance therapeutic management. In this context, a pooling of both fundamental and clinical research resources is needed .

The aim of this partnership is to create a synergy about cancer, with the ultimate goal of personalized care including a tumor ID card for each patient.

Le LYric s’articule autour de trois grands projets :

    • to understand the escape process of tumor cells from safeguard mechanisms and its role in resistance phenomenon. Three research areas will be developed for this purpose:
      • the study of the epithelial-mesenchymal transition (EMT), whose inductors are silenced in the adult stage and then reactivated in tumors. This reactivation could be an advantage to gain cellular plasticity, which allows escape and adaptation of tumor cells against therapies.
      • the study of the dependence receptors (DRs). Body cells are designed to occupy a given territory defined by the presence of their survival factors: cells are dependent of these factors and these factors are bounded by so-called dependence receptors (DRs). If the cell migrates outside its territory, the DR becomes unbound and triggers a cell death program, or apoptosis. The lost of receptor expression or the increase of ligand expression are considered as selective advantages by tumor cells, as for metastatic progression. That’s the reason why these events are often associated to bad prognosis when they are found in cancers.
      • the study of tumor cells dissemination processes, based on the knowledge of axonal guidance, where cells are shepherded by the presence or the absence of their ligand. The aim is to decipher how tumor cells turn away these pathways in order to migrate then to form metastasis in given places.
    • to develop molecules that are able to interact with targets identified, and then inhibit the tumor development. This is thanks to the cooperation between fundamental and clinical research. Clinical trials will be set up to evaluate the molecules efficiency.
    • to define genetic outlines from tumor biopsies, outlines which allow the identification of mutations in the tumor and the adaptation of the therapy according to them (please see below). In parallel, empiric works will be done to identify polymorphisms which may be involved in development and/or progression of tumors.

A l’heure actuelle, cette synergie est déjà opérationnelle puisque de nombreux essais cliniques entrent en phase II et III au sein des partenaires du LYric

 

Inside-cell abnormality study

If cancer remains as a major public health problem, several advances have enhanced the prognosis and the treatment of patients.

These advances result both of works on therapy resistance phenomenon and on the improvement of cures. This requires not only deciphering tumor resistance mechanisms but also a genetic analysis of different sorts of tumors, thanks to closely interaction between clinicians and scientists.

The LYric’s (Lyon Research Innovation for Cancer) aim is to pool research efforts to create a synergy able to:

  • understand tumor growth and tumor resistance pathways,
  • design clinical trials based on the identification of new targets thanks to fundamental research,
  • lead to personalized care, with a tumor ID card for each patient.

This synergy is already at work, as many clinical trials are underway in the LYric’s partners network(lien partenaires).

Clinical Studies

Profiler and MOST: a key path to personalized medicine

For an innovative medicine

The development of both targeted therapies in oncology since 15 years and high-throughput genomic technologies allow henceforth proposing to patients a treatment that specifically targets the genetic disorders identified in their tumor (personalized medicine).

Two academic clinical trials sponsored by the Centre Leon Berard (CLB) in the context of the LYric project (Principal Investigator: Pr Jean-Yves BLAY) will enable to develop this new concept of personalized medicine in oncology. The long term purpose is to extend the scope of prescription for existing targeted therapies and to give new perspectives to patients without any therapeutic option.

For personnalized medicine: practicable studies

It’s known that abnormality of the tumor cells is the cause of the development of some kind of cancer. Development of both « targeted » therapy in oncology since 15 years and high-Throughput genomic technologies are now used to propose to the patiens treatments that specifically targets the genetic disorders identified in the tumor.  Two academic clinical trials sponsored by the Centre Leon Berard (CLB) in the context of the LYric project will enable to develop this new concept of personalized medicine in oncology. The long term purpose is to give new perspectives to patients without any therapeutic option.

ProfiLER (Profilage LYric et Région)

The first one is ProfiLER, a cohort study which aims to collect tumor and blood samples in 2000 patients with a solid or hematologic advanced tumor, in order to establish the genetic profile of the tumor.

This genetic profile consists in a search for point mutations/insertions/deletions, gene copy number variations and chromosomic rearrangements in the tumor DNA using high throughput technologies available on the CLB’s technical platforms and for a predefined list of cancer genes.

Profiler-prog1-simplifie-anglais

A multidisciplinary molecular board has been set up in CLB to examine these profiles and to provide therapeutic recommendations based on the observed genetic alterations.
The study is opened in Centre Léon Bérard since February 2013 and opening in the Hospices Civils de Lyon (in the medical oncology departments of Edouard Herriot and Lyon Sud hospitals) is planned later in the year.

The first one, ProfiLER, aims to propose a tumor ID Card for the 2000 patients with all kind of cancer, with their express consent. The medical oncologist will be able to adapt the treatment to the patient, depending of the detected alteration of the tumor.

The study is opened in Centre Léon Bérard since February 2013 and opening in the Hospices Civils de Lyon  (in the medical oncology departments of Edouard Herriot and Lyon Sud hospitals) is planned later in the year.

Profiler-prog1-simplifie-anglais

MOST (Adaptation of the treatment)

The second study, MOST (My Own Specific Treatment) follows on from ProfiLER. MOST is a phase II trial conducted in adult patients with an advanced solid tumor in progression after at least 1 prior systemic treatment regimen.

The study aims to assess whether a 12-week treatment with a targeted therapy  based on the detected alteration in the tumor is sufficient to stabilize the disease (and even to increase survival) compared with a longer treatment, for all patients presenting this alteration, regardless of the primary disease site or cancer type.

Each enrolled patient will receive the adequate targeted therapy during 12 weeks (induction treatment). At the end of this period, patients with a tumor response will continue the targeted therapy, patients in progression will discontinue the targeted therapy and will be withdrawn from study and oriented towards standard treatments. Patients with a stable disease at 12 weeks will be randomized in order to determine if they continue or stop the targeted therapy. About 80 patients will be treated in each treatment group opened to enrollment, each group corresponding to an available targeted therapy.

most-prog1-Anglais

The study will open in summer 2013 in Centre Léon Bérard and in 2 other sites (Hospices Civils de Lyon and Institut Curie, Paris ) in a second time.

A biological sample collection (tumor and blood) is planned for both studies for medical and scientific research purposes, with the collaboration of the biological sample management platform (PGEB) and the Immunomitoring and Innovation in Immunology Platform (PI3) in CLB.

The second study, MOST (My Own Specific Treatment) follows on from ProfiLER. MOST is a phase II trial conducted in adult patients with an advanced solid tumor in progression after at least 1 prior systemic treatment regimen.

The study aims to assess whether a 12-week treatment with a targeted therapy based on the detected alteration in the tumor is sufficient to stabilize the disease (and even to increase survival) compared with a longer treatment.

Continuation of targeted therapy, according to established standards will depend on the evolution of the disease after the 12-week initial treatment (improvement, stabilization or progression of the disease).
The study will open in summer 2013 in CLB, and in Hospices Civils de Lyon and the Curie Institute of Paris in a second time.

most-prog1-Anglais

A biological sample collection (tumor and blood), with express consent of patient, is planned for both studies for medical and scientific research purposes, in order to improve diagnosis and cancer treatment.