Two researchers from Cancer Center Amsterdam received funding from the KWF Exploration call. Projects within this call focus on fundamental questions within oncology: how does cancer arise, grow and metastasize and how can we intervene in these processes? Topics include the immune system, the tumor microenvironment, metastatic behavior, DNA repair, liver fattening and an animal-free culture techniques. All studies provide indispensable knowledge for new breakthroughs in cancer prevention, detection and treatment. Congratulations to Maarten Bijlsma and Renske Steenbergen.

Maarten Bijlsma has received funding for his project into contributions of the tumor microenvironment to cancer stemness and therapy resistance in gastroesophageal adenocarcinoma. Renske Steenbergen has received funding for her project researching the validation of miRNA/mRNA regulators of anchorage-independent growth in clinically relevant in vitro models: towards reliable cancer risk stratification and improved treatments of HPV-induced anogenital precancers.

M. Bijlsma_Fred van Diem
Maarten Bijlsma on the importance of his research

"The incidence of esophageal cancer is rising sharply in the Western world, including the Netherlands, and remains a major cause of cancer-related mortality. Research from Amsterdam UMC and LUMC has identified several resistance mechanisms that hinder effective treatment. One of these mechanisms is the abundant presence of non-tumor cells and support tissue that is called the stroma. The stroma can have both tumor-suppressing and tumor-promoting effects, so inhibiting it has not been successful in the clinic.

Cancer-associated fibroblasts (CAFs) are the main cells in the stroma. Recent research suggests that different subgroups of CAFs exist and that their activities in the tumor environment vary. It is possible that this affects populations of resistant cancer cells and thus the response to treatments.

In the awarded KWF project, we will determine whether these subgroups of CAFs are present in esophageal cancer, understand their contribution to resistant cancer cells, and identify potential treatments to inhibit their tumor-promoting activities.

For this study, we will use existing gene expression datasets and the association of these data with clinical outcomes. We will also investigate the presence of these CAF subgroups in tumors and in a novel minitumor tissue model using advanced microscopic techniques, and study their effect on cancer cells. Furthermore, we are looking for potential drugs to inhibit the tumor-promoting role of CAFs. We aim to find candidate targets that can already be inhibited by existing agents, and prepare them for testing in clinical trials."

Renske Steenbergen on the importance of her research
"Infection with high-risk human papillomavirus (HPV) may cause cancer of the anogenital tract, including cervical, anal, and vulvar cancers. These cancers develop through premalignant stages. High-grade premalignant disease of the anogenital tract is diagnosed in ~10.000 patients in the Netherlands annually. Only a minority (~10-30%) is expected to progress to cancer. However, most patients are treated, as currently no reliable prognostic biomarkers are available to decide which patients should undergo treatment to prevent cancer. As a result, many patients are overtreated, which comes with unnecessary adverse health effects. Recognition of the advanced premalignant lesions with a high risk of progression to cancer is essential to improve clinical management of affected patients, and to prevent overtreatment in case of a low cancer risk.

We showed that progression of premalignant disease to cancer is accompanied by the accumulation of molecular aberrations. To define the biologically relevant molecular events driving carcinogenesis we studied which genes are functionally involved in the acquisition of anchorage independence in vitro. Anchorage independence is a hallmark of cancer allowing cells to grow without attachment and thus enabling invasion, meaning progression to cancer.

This project aims to functionally validate the role of these genes in the progression of premalignant disease to cancer. We will establish and utilize 3D models that accurately recapitulate in vivo conditions: organotypic raft cultures (ORCs) and patient-derived organoids (PDOs)."

Funding

This study was funded by the Dutch Cancer Society (KWF).

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