XenTech presents 7 posters at AACR 2018

 

 

 

Abstract Number: 919

Endogenous STING inhibition induces breast cancer cell death

Date and Time: Sunday Apr 15, 2018; 1:00 PM – 5:00 PM

Location: Poster Section 41

Poster Board Number: 26

A current cancer immunotherapy strategy proposes the use of STING agonists to boost the patient’s immune system through the cytokine-mediated enhancement of tumor infiltration and killing by immune cells. Using breast cancer cell lines including those derived from patient-derived xenografts, we show that STING clustering at DNA breaks in the nucleus is a general feature of breast cancer cells exposed to genotoxic agents, and that the STING pathway is a cell-intrinsic mechanism of cell survival. This study points up potentially antagonistic effects of STING pathway manipulation in tumor control.

 

 

 

Abstract Number: 2147

Development of preclinical models to accelerate the identification of next generation treatments for patients with acquired resistance to targeted therapies

Date and Time: Monday Apr 16, 2018; 1:00 PM – 5:00 PM

Location: Poster Section 7

Poster Board Number: 2

Patients whose tumor harbor specific driver molecular alterations benefit from targeted therapies but responses are generally short-lived due to the emergence of adaptive/secondary resistance. The MATCH-R trial led by Gustave Roussy, Villejuif, France (NCT02517892) will enroll 600 patients treated with targeted therapies. Biopsies obtained from 300 patients at resistance will be used to develop PDX models. This first report features PDX models with acquired resistance to last-generation therapies such as osimertinib, erdafitinib or trametinib. The MATCH-R PDX platform is being regularly upgraded with new models, providing a unique resource to unravel the mechanisms involved in acquired resistance to targeted therapies and develop novel therapeutic strategies translating into increased patient survival.

 

 

 

Abstract Number2811

High IFN/STAT-related gene expression is associated with sensitivity to PARP inhibitors of triple negative breast cancer

Date and Time: Monday Apr 16, 2018; 1:00 PM – 5:00 PM

Location: Poster Section 37

Poster Board Number: 1

Pathogenic BRCA1/2 mutations and other genomic alterations are hallmarks of cancers with homologous recombination deficiency (HRD) that are more likely to be sensitive to PARP inhibitors (PARPi). However, these markers lack specificity as less than half of patients harboring BRCA-mutated or HRD-positive tumors are responsive to PARP inhibitors, and a number of tumors without BRCA1/2 mutations are responsive to PARPis. In vivo efficacy of PARPis was tested in a panel of 53 TNBC PDX models characterized for BRCA1/2 or HRD status and a gene expression classifier was built that improved the accuracy of the BRCA and HRD assays in predicting PARPi responsiveness.

Abstract Number4628

Tailoring personalized strategies for children with treatment-refractory liver cancer

Date and Time: Tuesday Apr 17, 2018; 1:00 PM – 5:00 PM

Location: Poster Section 29

Poster Board Number: 1

Hepatoblastoma (HB) is a rare paediatric tumor for which it is difficult to set up clinical trials. We developed a panel of 24 HB PDX models and 10 corresponding PDX-derived cell lines as a translational platform for the development of novel therapeutic options for children with HB. Here we show that volasertib, an inhibitor of the PLK1 oncogene that is overexpressed in HB, displays a good efficacy profile, comparable to that of the temozolomide/irinotecan combination.

 

Abstract Number: 5600

Establishment and characterization of a unique circulating tumor cells-derived xenograft (CDX) in prostate cancer

Date and Time: Wednesday, April 18; 8:00 AM-12:00 PM

Location: Poster Section 27

Poster Board Number: 3

We report the development of a unique PDX model from the CTCs of a patient with advanced prostate cancer (PCa). While demonstrating the tumorigenicity of CTCs from PCa, this CDX model represents a unique tool to identify clonal mutations associated with the tumor-initiating capacity of CTCs and explore the genetic and phenotypic basis of metastasis and drug resistance in advanced PCa.

 

Abstract Number: 1718

Tumor immune gene profile before and after various targeted therapies in NSCLC PDXs

Date and Time: Monday Apr 16, 2018; 8:00 AM – 12:00 AM

Location: Poster Section 32

Poster Board Number: 13

Using a panel of non-humanized NSCLC PDXs, we have identified specific tumor immune profiles and a set of genes involved in the response to targeted therapies. Pharmacodynamic analysis of immune markers reveals potential combinations of targeted therapies with immune checkpoints blockade that may have important translational value.

 

Abstract Number: 2597

Development and characterization of novel non-small cell lung cancer (NSCLC) circulating tumor cells (CTCs)-derived xenograft (CDX) models

Date and Time: Monday Apr 16, 2018 1:00 PM – 5:00 PM

Location: Poster Section 25

Poster Board Number: 27

We describe the establishment and characterization of 4 CDX models from advanced NSCLC patients. This study revealed both similarities and differences between CDXs and their corresponding patient tumor biopsies. These NSCLC CDX models represent unique tools to identify clonal mutations associated with the tumor-initiating capacity of CTCs and explore the genetic and phenotypic basis of metastasis and drug resistance associated with advanced NSCLC.