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Presentation of SIRIC research to the international community at the AACR 2019 congress

SIRIC team
SIRIC's work at AACR 2019
AACR Annual Meeting 2019

The American Association for Cancer Research (AACR) is one of the biggest events dedicated to cancer research. Research in the frame of the SIRIC program was presented by the clinician/researchers from Institut Curie. 

PLK1: a new therapeutic target for hormone-resistant ER positive breast cancers

Elisabetta Marangoni presented the results of her research on preclinical models of bone metastases from luminal breast cancer

The work was carried out in the Preclinical Investigation Laboratory supported by the SIRIC in collaboration with multiple doctors and geneticists from the hospital and the research centre (Guillaume Dutertre, Paul Cottu, Ivan Bièche, Anne Salomon). It concerns PLK1 as a new therapeutic target for hormone-resistant ER postive breast cancers.

The treatment of xenografts established from biopsies of bone metastases taken from patients with an aggressive breast cancer with a PLK1 inhibitor resulted in complete responses. This same treatment was shown to be very effective in preclinical models of acquired palbociclib resistance (CDK4/6 inhibitor) and is therefore of major clinical interest. 

MBD4 inactivation leads to an alternative evolution pathway in uveal melanoma

Marc-Henri Stern presented the work of the uveal melanoma (UM) team evaluating UM heterogeneity by sequencing 16 primary tumor samples and 75 metastases samples from 25 patients. The team describe two classes of tumors depending on the status of the MBD4 gene that have different genetic evolutions. 

UM's not mutated for MBD4 are homogenous tumors acquiring few new mutations - of which no new oncogenic mutation - during metastatic progression. However, several recurrent copy number alterations are acquired during the metastatic process. 

MBD4 deficient UM are hypermuted, associated with a very high genetic heterogeneity and new oncogenic mutations. The copy number alteration profiles are similar to those of tumors not mutation for MBD4. 

The conclusions: 

  1. The homogeneity of UM that is not mutated by MBD4, by far the most frequent, excludes tumor heterogeneity as a resistance mechanism to treatments;
  2. this absence of heterogeneity predicts lasting responses to targeted therapies when these are identified;
  3. the continuous acquisition of mutations in the context of a mutated MBD4 gene reveals the chronology of oncogenic events in these tumors 

Circulating tumor cells and circulating tumor DNA in advanced ER positive breast cancers

François-Clément Bidard presented the national clinical trials initiated by Institut Curie on circulating biomarkers to improve the treatment choise for women with certain metastatic breast cancers that are particularly difficult to treat. 

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