Publications by authors named "P Bouwman"

The discovery of and as tumor susceptibility genes and their role in genome maintenance has transformed our understanding of hereditary breast and ovarian cancer. This review traces the evolution of BRCA1/2 research over the past 30 years, highlighting key discoveries in the field and their contributions to tumor development. Additionally, we discuss current preventive measures for mutation carriers and targeted treatment options based on the concept of synthetic lethality.

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Background: Understanding the variability across the human population with respect to toxicodynamic responses after exposure to chemicals, such as environmental toxicants or drugs, is essential to define safety factors for risk assessment to protect the entire population. Activation of cellular stress response pathways are early adverse outcome pathway (AOP) key events of chemical-induced toxicity and would elucidate the estimation of population variability of toxicodynamic responses.

Objectives: We aimed to map the variability in cellular stress response activation in a large panel of primary human hepatocyte (PHH) donors to aid in the quantification of toxicodynamic interindividual variability to derive safety uncertainty factors.

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Carcinogenic chemicals, or their metabolites, can be classified as genotoxic or non-genotoxic carcinogens (NGTxCs). Genotoxic compounds induce DNA damage, which can be detected by an established and battery of genotoxicity assays. For NGTxCs, DNA is not the primary target, and the possible modes of action (MoA) of NGTxCs are much more diverse than those of genotoxic compounds, and there is no specific assay for detecting NGTxCs.

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Article Synopsis
  • Triple-negative breast cancer (TNBC) is challenging to treat due to its aggressive nature and limited options, prompting research into CDK inhibitors like THZ531 for potential synergistic effects with other anti-cancer drugs.
  • Studies involved combining various kinase inhibitors with CDK inhibitors in TNBC cell lines to find effective treatments, using techniques like CRISPR-Cas9 knockout and RNA sequencing to understand resistance mechanisms.
  • Results showed that many tyrosine kinase inhibitors work well with THZ531, and the multidrug transporter ABCG2 was identified as a key factor in resistance; when inhibited, it enhances cell sensitivity to CDK inhibitors.
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