New-generation technologies for spatial tissue analysis, indispensable tools for deciphering intratumor heterogeneity in the development of antibody-drug conjugates and radio-immunoconjugates for cancer treatment.

Technologies allowing tissue molecular analysis of the "high-plex" type (>20 molecules per tissue section) are the 21 century inventions that are revolutionizing our knowledge of the biology of malignant tumors and many benign alterations. These technologies are based on specific probe labeling systems for the detection of tissue components [proteins, messenger RNA (mRNA)], as well as on detailed image analysis, combined with computational tools. We are synthetically presenting technologies based on image analysis, such as multiplex immunofluorescence (mIF), imaging mass cytometry (IMC), and multiplexed ion beam imaging (MIBI), as well as the ones not based on image analysis, such as multiplex in situ hybridizations (ISHs) using various principles.

Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis.

AXL receptor tyrosine kinase has been described as a relevant molecular marker and a key player in invasiveness, especially in triple-negative breast cancer (TNBC). We evaluate the antitumor efficacy of the anti-AXL monoclonal antibody 20G7-D9 in several TNBC cell xenografts or patient-derived xenograft (PDX) models and decipher the underlying mechanisms. In a dataset of 254 basal-like breast cancer samples, genes correlated with expression are enriched in EMT, migration, and invasion signaling pathways.

HER3 as biomarker and therapeutic target in pancreatic cancer: new insights in pertuzumab therapy in preclinical models.

The anti-HER2 antibody pertuzumab inhibits HER2 dimerization and affects HER2/HER3 dimer formation and signaling. As HER3 and its ligand neuregulin are implicated in pancreatic tumorigenesis, we investigated whether HER3 expression could be a predictive biomarker of pertuzumab efficacy in HER2low-expressing pancreatic cancer. We correlated in vitro and in vivo HER3 expression and neuregulin dependency with the inhibitory effect of pertuzumab on cell viability and tumor progression.