Breaking Resistance, Shaping the Future | Research Voices (Episode 6) - Prof. Paul Hofman, IHU RespirERA

Prof. Paul Hofman Reflects on Liquid Biopsy, Multi-Omics Integration, and Ultra-Stratified Personalized Medicine in Thoracic 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 Paul Hofman, a globally recognized authority in pathology and thoracic oncology, Director of the Laboratory of Clinical and Experimental Pathology at Nice University Hospital, and Director of IHU RespirERA

In this engaging conversation, Prof. Hofman discusses the critical role of liquid biopsy as an indispensable "piece of the puzzle" alongside tissue biopsy and multi-modal imaging (CT and PET scans) in thoracic oncology. He explores the clinical imperative for decentralized testing rather than sole reliance on outsourcing to streamline turnaround times for patients. Furthermore, Prof. Hofman provides deep mechanistic insights into the integration of plasma-derived multi-omics - including methylomic signatures and proteomics - with epidemiological and clinical-associated annotations to track mutations associated with resistance and usher in an era of ultra-stratified personalized medicine.

Watch the Full Interview

Interview Highlights

• The complementary role of liquid biopsy alongside tissue biopsy, CT scans, and PET scans in thoracic oncology
• The clinical necessity of decentralization in liquid biopsy testing to reduce turnaround time and avoid full outsourcing
• Detecting resistance-associated mutations and tracking minimal residual disease (MRD) using real-world plasma samples
• Integrating plasma methylomic signatures, proteomics, and multi-omics to advance therapeutic decision-making
• Leveraging epidemiological and clinical-associated annotations to build robust predictive models
• Moving toward ultra-stratified personalized medicine to overcome drug resistance in lung cancer

Key Takeaways

Completing the Diagnostic Puzzle via Liquid Biopsy

Prof. Hofman highlights that while tissue biopsy remains a cornerstone, liquid biopsy using plasma samples provides critical, real-time insights into tumor dynamics. Rather than replacing traditional imaging like CT and PET scans or tissue pathology, liquid biopsy serves as a vital piece of the diagnostic puzzle. It enables clinicians to assess spatial and temporal tumor heterogeneity, monitor minimal residual disease (MRD) in real-world thoracic oncology settings, and identify mutations associated with therapy resistance in a minimally invasive manner.

Advancing Decentralization over Outsourcing

Addressing the clinical implementation of liquid biopsy, Prof. Hofman emphasizes the importance of decentralization. To significantly shorten turnaround time and ensure rapid clinical decision-making, hospital pathology and molecular labs must develop in-house testing capabilities rather than relying exclusively on outsourced centralized facilities. Establishing decentralized, standardized liquid biopsy workflows directly within clinical centers is essential for bringing precision medicine closer to the patient.

Pioneering Ultra-Stratified Personalized Medicine

Prof. Hofman reflects on the future of biomarker discovery, stressing that single-gene testing is no longer sufficient to address complex resistance mechanisms. The next frontier lies in multi-omics integration - combining plasma DNA methylomic signatures, proteomics, and comprehensive genomic profiling with detailed epidemiological and clinical annotations. By merging these multi-dimensional data layers, researchers and clinicians can achieve what he terms "ultra-stratified personalized medicine," tailoring treatments with unprecedented precision.

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