Breaking Resistance, Shaping the Future | Research Voices (Episode 8) - Prof. Martine Piccart, Université libre de Bruxelles，Institut Jules Bordet
Prof. Martine Piccart Reflects on ADC Resistance Mechanisms, Biomarker Bottlenecks, the OASIS Consortium, and the Data-Sharing Imperative in Precision Oncology
As part of Breaking Resistance, Shaping the Future, a scientific series celebrating the eighth anniversary of Cancer Drug Resistance (CDR), the journal is pleased to present the latest episode of Research Voices, an interview series spotlighting leading scientific experts and clinical pioneers from around the world.
This episode features Professor Martine Piccart, a distinguished leader in global oncology. Currently serving as Honorary Professor of Oncology at Université Libre de Bruxelles (ULB) and Scientific Director at the Institut Jules Bordet, Prof. Piccart is also the Co-founder of the Breast International Group (BIG). As a member of the Belgian Royal Academy of Medicine, her influential career includes having served as President of major international societies, including ESMO, ECCO, and EORTC.
In this engaging conversation, Prof. Piccart discusses the rapidly evolving landscape of Antibody-Drug Conjugates (ADCs) and the substantial gaps that remain in understanding their mechanisms of response and resistance. She highlights pressing clinical dilemmas, including the management of severe treatment toxicities (such as T-DXd-induced interstitial lung disease) and the complete lack of standardized evidence regarding optimal ADC sequencing. Furthermore, Prof. Piccart shares insights into Europe’s landmark OASIS academic consortium, the critical shortage of robust diagnostic biomarkers across currently approved ADCs, and why overcoming pharmaceutical data silos through open data sharing and artificial intelligence is the single most vital hurdle to clear in the fight against cancer drug resistance.
Watch the Full Interview
Interview Highlights
1. Current limitations in unraveling ADC resistance mechanisms and managing heightened drug toxicity (e.g., T-DXd-induced interstitial lung disease)
2. Major clinical bottlenecks: personalizing ADC selection and defining rational ADC sequencing strategies post-resistance
3. The European OASIS consortium: leveraging multi-parametric modeling, Immuno-PET imaging, patient-derived organoids, and proteomics
4. The severe shortage of robust, standardized biomarkers across T-DM1, T-DXd, and Sacituzumab Govitecan
5. Breaking down data silos: balancing pharmaceutical investment with mandatory academic data access for AI and machine learning applications
6. Fostering the next generation of academic leaders through early-career editorial initiatives and scholarly commentary
Key Takeaways
Unraveling ADC Resistance and Clinical Sequencing Bottlenecks
Prof. Piccart underscores that despite the remarkable therapeutic success of modern ADCs, academic understanding of their underlying resistance mechanisms remains surprisingly early and limited. As newer ADCs deliver higher potency, clinicians are also confronted with increased toxicity risks, such as potentially fatal interstitial lung disease (ILD) associated with T-DXd. Crucially, oncology practice lacks established guidelines for personalizing ADC choice or determining the optimal order of ADC administration once a patient progresses. To address these challenges, academic efforts like the European OASIS consortium - coordinated by Dr. Barbara Pistilli - are adopting multi-parametric approaches. By combining HER2/NECTIN4/TROP2 Immuno-PET imaging, patient-derived organoid models, digital pathology, circulating tumor cells (CTCs), and saliva/plasma proteomics, OASIS aims to systematically decipher mechanisms driving resistance and drug toxicity.
Navigating the Critical Shortage of Diagnostic Biomarkers
Addressing current diagnostic limitations, Prof. Piccart stresses that precision oncology currently operates under a severe deficit of reliable biomarkers for ADCs. While HER2-PET target imaging provides valuable insights into target density and spatial expression homogeneity for T-DM1, agents such as T-DXd exhibit therapeutic activity even in HER2-low tumors without clear predictive biomarkers. Similarly, while TROP2 expression correlates with response to Sacituzumab Govitecan, the absence of standardized testing protocols leaves clinicians administering therapy without actionable biomarker guidance. Developing robust, reproducible assays is essential to properly select patient populations and prevent unnecessary toxicities.
Democratizing Data Access and Harnessing AI for Future Breakthroughs
Looking toward the future of the field, Prof. Piccart identifies data access and inter-institutional sharing as the primary non-technical barriers to overcoming treatment resistance. Because major clinical trials are predominantly funded and controlled by pharmaceutical companies, valuable patient datasets and biospecimens remain isolated in proprietary silos. Academic centers, conversely, lack the financial resources to independently run massive multi-center trials. Prof. Piccart advocates for novel frameworks that protect pharmaceutical innovation while mandating open data sharing for academic research post-trial. Pooling data from thousands of trial participants is indispensable for training artificial intelligence and machine learning models capable of predicting resistance and guiding multi-agent combination strategies.
This interview marks a key installment of the Research Voices series. Stay tuned for upcoming conversations with leading experts as we continue to explore the theme Breaking Resistance, Shaping the Future.
Editor: Stella Jin
Language Editor: Amir Khan
Production Editor: Xingyue Luo
Respectfully Submitted by the Editorial Office of Cancer Drug Resistance
