Precision medicine strategies for patients with metastases of colorectal carcinoma resistant to treatments

Despite considerable progress in the therapeutic treatment of cancer patients, the vast majority of them face a relapse of their disease due to the development of drug resistance mechanisms.

We need to explore new approaches to counteract the emergence of such resistance and enable broad-spectrum treatments to maintain their efficacy without additional cytotoxicity. In particular, we want to investigate the importance of transient reprogramming in response to stress (treatment is considered a stress to the tumor) and how this might impact tumor spread. To this end, we will use relevant preclinical models that also take into account the role of the tumor microenvironment.

We are looking for a talented and experienced PhD researcher to work on resistance to novel treatments for aggressive/metastatic cancers (colon or PDAC).

Ideally, our mid-term goal is to propose the candidate for the national INSERM/CNRS competition within 3 years and make him/ her a permanent researcher of the team to lead ambitious projects on the proposed topic (optional)

In the meantime, we will jointly apply for a European grant (DL: MSCA Sept 2023, ARC Post-doc in France, Fondation de France fellowships).

Environment

Co-team leaders: E Mamessier (scientist, immunologist and expert in conducting translational studies at INSERM) and F Bertucci (oncologist, Institut Paoli Calmettes, Marseille, France). This joint leadership allows us to combine technical development and the exploration of new scientific topics with relevant clinical questions and access to patient samples. This has proven successful in the past and we would like to maintain this by forming a team of clinicians and scientists to lead a project.

The team consists of about 17 people: 5 clinicians (surgeon, oncologist, pathologist, all part-time), 3 computer analysts, 2 molecular technicians, 3 cell technicians, 2 lab assistants, 2 PhD students. A full-time scientist/biologist to work with the clinicians in the team on ambitious translational projects is currently sorely lacking and we are looking to strengthen our team.

The team is fully equipped for next generation sequencing (Nextseq500), pan-transcriptomic analysis (Affy), comparative genomic hybridization (Agilent), isolation and analysis of circulating tumor DNA (BioRad), isolation and analysis of circulating tumor cells (Parsortix) and microfluidic devices (Ibidi, Fluigent, ..).

We have established in silico gene expression databases with annotated clinical data, which are among the largest databases available today. We have also created our own bulk and single cell datasets and associated analysis pipeline.

We conduct prospective clinical trials that provide us with fresh blood and tumor samples to derive preclinical models (organoids from patient tumors, patient-derived xenografts).

If necessary, we also develop our own therapies (ADC or ASO).

We combine all these tools/technologies to develop precision medicine strategies in metastatic colorectal or breast cancer. Our goal is to improve overall survival in metastatic cancer through better classification of tumors, more therapeutic options, better targeting and a better understanding of resistance mechanisms to treatments.

The core of the team’s activity relies on prospective or retrospective studies that provide us with fresh blood and tumor samples to create preclinical models (e.g. patient tumor-derived organoids or patient-derived xenografts) and perform in-depth molecular characterization of tumors derived from FFPE tissue. These samples are unique and valuable and help us to investigate therapy resistance.