Catherine Alix-Panabières: A Highly Active Researcher (CTC)

If Montpellier University Hospital has gained international expertise in liquid biopsy, it owes it to Catherine Alix-Panabières. The woman who pioneered the use of blood tests for cancer diagnosis 25 years ago can now take pride in the fact that there isn’t a single oncology conference today that doesn’t include a session on the subject. This international recognition is evidenced by the numerous awards listed on her resume, including two prizes from the National Academy of Medicine in 2012 and 2023,the International Liquid Biopsy Society Award , andthe Alexandr Savchuk Award. She makes no secret of her delight at playing in the big leagues. “I find it exceptional to have been able to exchange ideas with a scientific figure of the stature of the 2018 Nobel Prize in Medicine, Professor Tasuku Honjo,” she says, recalling her meeting this year in Japan at Kyoto University with the renowned immunologist.

Starting with her postdoctoral work in 1999, which took place at both the University Hospital and the University of Montpellier, Catherine Alix-Panabières pioneered research in France on the detection of circulating tumor cells (CTCs) in solid tumors. Certain more aggressive cells break away from cancerous tumors and travel through the bloodstream to reach other organs (liver, bone, lung, brain, etc.), where they create micrometastases and then metastases. The study of these cells that spread cancer quickly proved promising from a therapeutic standpoint for establishing a prognosis for the disease.

First patent

This scientist filed her first patent in 2002 and began to make a name for herself on the international stage.“Professor Klaus Pantel from the University of Hamburg spotted me at an international conference,” says the researcher, who has collaborated with him ever since and is now a visiting professor at the German university. It was in a joint publication (Circulating Tumor Cells in Cancer Patients: Challenges and Perspectives, in 50 Trends in Molecular Medicine, 2010) that the two researchers coined the term “liquid biopsy” in 2010.

But local recognition was slow in coming.“My work was initially met with a healthy dose of skepticism,” she puts it mildly. She believed in it wholeheartedly and found the means to fund her research and her position for eleven years, working under a contract between the University Hospital and the University of Montpellier.“I raised a total of over 13 million euros to fund the equipment and research work of my laboratory; the LCCRH is one of a kind in Europe.” Unique for the diversity of cancers studied—some fifteen types, including breast, prostate, pancreatic, melanoma, and glioblastoma—but also for the numerous circulating biomarkers being investigated, which require an equal number of ad hoc cutting-edge technologies.

From discovery to clinical applications

“Liquid biopsy is evolving. It’s no longer just about identifying CTCs or circulating tumor DNA, but also all other tumor-induced biomarkers, such as immune system cells,” notes the researcher, who outlines the potential of a non-invasive test capable of deciphering the blood signature of biomarkers to diagnose cancer and its severity, but also to identify therapeutic targets and provide the most appropriate treatment, assess treatment efficacy and identify resistance mechanisms, and evaluate residual cancer prior to standard imaging. “Thisis what we call personalized medicine.”

In 2020, a study conducted at Montpellier University Hospital demonstrated, for the first time worldwide, the clinical utility of a liquid biopsy in selecting a treatment for metastatic breast cancer (Molecular and functional characterization of circulating tumor cells: from discovery to clinical application, in Clinical Chemistry, 2020). Indeed, this test is extremely sensitive in detecting CTCs: these cells remain in the blood for only a few hours, and their identification therefore accurately reflects tumor progression in real time. These indicators of cancer severity help determine whether chemotherapy is necessary.

Liquid biopsy and AI

Among the fifteen or so projects she is currently leading with her team and partners, a new flagship project focuses on identifying a blood biomarker for the very early detection of pancreatic cancer (Early detection of pancreatic cancer by liquid biopsy “Panlipsy”: a French nationwide study project, in Springer Nature Link, 2024).  “This is a major public health issue because the incidence of this cancer continues to rise, and the survival prognosis is very poor,” she emphasizes. The five-year survival rate for patients is, in fact, only 11%.

Here, the research protocol uses liquid biopsy and artificial intelligence:“In an initial phase known as the discovery phase, we use blood samples from several hundred patients with the disease to train the AI to identify the biomarker(s) characteristic of this cancer and to distinguish them from those of healthy subjects. The goal is to develop a robust decision-making algorithm.” In a second stage, or validation phase, processing data from liquid biopsies “from an independent cohort comprising cancer patients and healthy individuals will enable early diagnosis of pancreatic cancer using the previously trained algorithm,” explains the researcher.

Tumor spread

His team is also continuing its research into the biology of metastatic processes and the development of new technologies capable of detecting functional CTCs, which trigger metastatic disease (Mechanobiology and Survival Strategies of Circulating Tumor Cells: A Process Toward the Invasive and Metastatic Phenotype, in Frontiers in Cell and Developmental Biology, 2023). This is a critical issue, given that more than 90% of patients die from metastases rather than from the primary tumor.“Thanks to the in vitro culture of CTCs, we have succeeded in obtaining CTC lines that possess stem cell properties. This is a valuable breakthrough because it provides us with a unique tool for studying tumor dissemination and understanding how CTCs cause relapses. I hope our work will lead to one or more therapeutic approaches aimed at limiting tumor dissemination,” explains the professor.

We wrap up our interview to let Catherine Alix-Panabières finish up a new paper before flying to Sydney the next day. She is scheduled to deliver a keynote address at the^10th anniversary of the Thomas Ashworth CTC and Liquid Biopsy Symposium. But her list of activities is still long. In addition to the traditional teaching and mentoring responsibilities of a university professor, she participates in several conferences each month and organizes large-scale events, such as this fall’s co-organization of an international conference on liquid biopsy in San Diego through the prestigious American Association for Cancer Research (AACR). Or, more recently, her involvement in designing a major exhibition on cancer at the Cité des Sciences in Paris.“It’s a lot of different things to manage at the same time, but it also offers great intellectual freedom ,” says the woman whose international recognition takes her to all corners of the globe.