Van Neerven group

By uncovering the molecular mechanisms that govern competitive interactions during the earliest stages of cancer development, we aim to define principles that may inform future strategies for early intervention.

Tissues are dynamic ecosystems in which cells continuously compete for space and survival. When cells acquire oncogenic mutations, their relative fitness within this environment may change, thereby reshaping the clonal landscape of the tissue.

Our group investigates how oncogenic mutations influence cell competition and how this may promote tumour initiation. We study how competitive interactions between normal and mutant cells differ between developing organs in children and fully established tissues in adults, and how such context-dependent differences influence tissue-specific cancer susceptibility and tumour type across the lifespan.

How do mutant cells spread in developing tissues of children compared to adult homeostatic tissues? During development and postnatal growth, tissues expand, remodel, and reorganize, whereas adult tissues are maintained by tightly regulated homeostatic mechanisms that stabilize tissue composition. These fundamental differences may create unique windows of opportunity for mutant clones to persist or expand. We investigate how tissue growth, architecture, and stem cell dynamics define modes of cell competition and constraint, and how this influences the earliest steps of cancer development.

Why do germline mutations in cancer predisposition genes cause tumors in some tissues but not others, and why does cancer risk vary across life stages? Despite carrying the same inherited mutation, individuals develop tumors in highly tissue-specific and age-dependent patterns. We study how tissue-specific microenvironments shape cell competition and determine how effectively tissues cope with mutant clones. By understanding why certain tissues are better equipped to withstand mutant clone expansion, we aim to identify regulatory principles that could be harnessed to prevent tumor initiation in high-risk contexts.

Survivors of childhood cancer have a significantly increased risk of developing second malignant neoplasms, often many years after treatment. These late cancers frequently arise in epithelial tissues that were previously exposed to chemotherapy or radiotherapy. While therapy-induced mutations are often implicated, an underexplored possibility is that cytotoxic treatments may selectively promote the expansion of pre-existing mutant clones within developing tissues, thereby predisposing these tissues to cancer development years or decades later. We investigate how early-life cancer therapies alter clonal competition and long-term tissue regulation, and how these changes contribute to tumor initiation later in life.