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Carlo Bosi: Out on European Journal Of Cancer ‘Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response’

Photo taken from Carlo Bosi/Twitter

Oct 17, 2023, 18:11

Carlo Bosi: Out on European Journal Of Cancer ‘Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response’

Carlo Bosi, Medical oncology resident in Ospedale San Raffaele, shared a post on X/Twitter:

“Out on European Journal Of Cancer ‘Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response’

We searched clinicaltrials.gov for trials testing ADCs in solid tumors, and annotated them by ADC targets (n=54), type of payload and disease condition.

We investigated the mRNA expression of ADC targets and genes potentially implicated in treatment response/resistence to ADCs in large publicly available datasets

We assessed ADC target expression compared to healthy tissue across solid tumors. Tumor types with the highest ADCs target expression may represents unexplored opportunities for ADCs development

Metastases differed from primary tumors in expression of ADC targets, and this should be taken into account

Potential, not clinically proven, predictors of ADCs response/resistence (e.g. cathepsins, genes implied in cellular trafficking or sensitivity to cytotoxic cargo) are heterogeneously expressed, suggesting a different intrinsic sensitivity to ADCs

Breast cancer subtypes share most, but not all, ADC targets expression, which may pave the way for novel therapeutic opportunities, e.g. targeting ITGB6 and LRRC15 in HER2+ breast cancers

ADC targets with the highest differential expression compared to normal tissues may contribute to orient the development of ADCs in clinical trials

There is substantial inter-patient heterogeneity in ADC targets expression. This might be considered when multiple ADCs options, including agnostic registrations, are available in the clinic

Huge thanks to my mentor Giampaolo Bianchini Matteo Dugo co-lead of the study, the invaluable support of AirC and Ospedale San Raffaele, and the contributions of all the other co-authors, Aron Bartha, Barbara Galbardi, Giulia Notini, Matteo M. Naldini, Luca Licata, Giulia Viale“