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

If Montpellier University Hospital has international expertise in liquid biopsy, it is thanks to Catherine Alix-Panabières. The woman who pioneered the use of blood tests to diagnose cancer 25 years ago can now boast that there is not a single cancer conference that does not include a session on the subject. Her international recognition is attested to by the numerous awards listed on her CV, including two prizes from the French National Academy of Medicine in 2012 and 2023,the International Liquid Biopsy Society Award , andthe Alexandr Savchuk Award. She makes no secret of her pleasure 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 famous immunologist.

Since completing her postdoctoral studies in 1999, working between the University Hospital and the University of Montpellier, Catherine Alix-Panabières has pioneered research in France on the detection of circulating tumor cells (CTCs) for solid cancers. Some more aggressive cells break away from cancerous tumors and travel through the bloodstream to other organs (liver, bones, lungs, brain, etc.), where they create micrometastases and then metastases. The study of these cells that spread cancer quickly proved promising in terms of establishing a prognosis for cancer.

First patent

In 2002, this scientist filed her first patent and made 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 continued to collaborate 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 reasonable skepticism," she says euphemistically. She believed firmly in her work and found the means to finance her research and her position for eleven years, working under contract between the University Hospital and the University of Montpellier. "I raised a total of more than €13 million to finance the equipment and research work of my laboratory; the LCCRH is unique in Europe." It is unique in terms of the diversity of cancers studied, including around fifteen types of cancer, such as breast, prostate, pancreatic, melanoma, and glioblastoma, but also in terms of the numerous circulating biomarkers being researched, which require a corresponding number of cutting-edge technologies.

From discovery to clinical applications

"Liquid biopsy is evolving. It is no longer just a matter of identifying CTCs or circulating tumor DNA, but also all other tumor-induced biomarkers such as immune system cells," emphasizes the researcher, who lists the promises of a non-invasive test capable of decoding the blood signature of biomarkers to diagnose cancer and its severity, but also to identify therapeutic targets and provide the most appropriate treatment, evaluate the effectiveness of a treatment and identify resistance mechanisms, and assess residual cancer disease prior to standard imaging. "We're talking about personalized medicine."

In 2020, a trial conducted at Montpellier University Hospital demonstrated for the first time worldwide the clinical usefulness of liquid biopsy in choosing a treatment for metastatic breast cancer (Molecular and functional characterization of circulating tumor cells: from discovery to clinical application, in Clinical Chemistry, 2020). This test is extremely sensitive in detecting CTCs: these cells remain in the blood for only a few hours, so identifying them provides an accurate reflection of 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 involves searching for a blood signature to detect pancreatic cancer at a very early stage (Early detection of pancreatic cancer by liquid biopsy "Panlipsy": a French nation-wide study project, in Springer Nature link, 2024).  "This is an important public health issue because the incidence of this cancer continues to rise and the prognosis for survival is very poor," she emphasizes. The five-year survival rate for patients is only 11%.

Here, the research protocol uses liquid biopsy and artificial intelligence: "In an initial discovery phase, blood samples from several hundred patients are used to train the AI to identify the biomarker(s) characteristic of this cancer and distinguish them from those of healthy subjects. The goal is to obtain a robust decision-making algorithm." In a second stage, or validation phase, the processing of liquid biopsy data "from an independent cohort composed of cancer patients and healthy subjects will enable early diagnosis of pancreatic cancer, thanks to the previously trained algorithm," explains the researcher.

Tumor dissemination

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 initiate metastatic disease (Mechanobiology and survival strategies of circulating tumor cells: a process towards the invasive and metastatic phenotype, in Frontiers in Cell and Developmental Biology, 2023). This is a significant challenge, given that more than 90% of patients die from metastases rather than from the initial tumor. "Thanks to the in vitro culture of CTCs, we have succeeded in obtaining CTC lines that have stem cell properties. This is a valuable breakthrough because it provides us with unique material for studying tumor dissemination and understanding how CTCs cause relapses. I hope that our work will lead to one or more therapeutic approaches aimed at limiting tumor dissemination," explains the professor.

We end our interview to let Catherine Alix-Panabières finish up a new communication before flying to Sydney the next day. She is expected to give a keynote lecture at the^10th anniversary of the Thomas Ashworth CTC and liquid biopsy symposium conference. But her list of activities is still long. In addition to her traditional teaching and supervisory duties as 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). More recently, she helped design a major exhibition on cancer at the Cité des Sciences in Paris. "It's a lot of different things to juggle, but it also gives me great intellectual freedom," says the woman whose international recognition has taken her to the four corners of the globe.