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AbstractTaxanes and platinum molecules, specifically paclitaxel and carboplatin, are widely used anticancer drugs that induce cell death and serve as first‐line chemotherapy for various cancer types. Despite the efficient effect of both drugs on cancer cell proliferation, many tumours have innate resistance against paclitaxel and carboplatin, which leads to inefficient treatment and poor survival rates. Haploid human embryonic stem cells (hESCs) are a novel and robust platform for genetic screening. To gain a comprehensive view of genes that affect or regulate paclitaxel and carboplatin resistance, genome‐wide loss‐of‐function screens in haploid hESCs were performed. Both paclitaxel and carboplatin screens have yielded selected plausible gene lists and pathways relevant to resistance prediction. The effects of mutations in selected genes on the resistance to the drugs were demonstrated. Based on the results, an algorithm that can predict resistance to paclitaxel or carboplatin was developed. Applying the algorithm to the DNA mutation profile of patients' tumours enabled the separation of sensitive versus resistant patients, thus, providing a prediction tool. As the anticancer drugs arsenal can offer alternatives in case of resistance to either paclitaxel or carboplatin, an early prediction can provide a significant advantage and should improve treatment. The algorithm assists this unmet need and helps predict whether a patient will respond to the treatment and may have an immediate clinically actionable application. Show less

The Keap1-Nrf2 signaling pathway plays a crucial role in cellular defense against oxidative stress-induced damage. Its activation entails the expression and transcriptional regulation of several proteins involved in detoxification and antioxidation processes within the organism. Keap1, serving as a pivotal transcriptional regulator within this pathway, exerts control over the activity of Nrf2. Various post-translational modifications (PTMs) of Keap1, such as alkylation, glycosylation, glutathiylation, S-sulfhydration, and other modifications, impact the binding affinity between Keap1 and Nrf2. Consequently, this leads to the accumulation of Nrf2 and its translocation to the nucleus, and subsequent activation of downstream antioxidant genes. Given the association between the Keap1-Nrf2 signaling pathway and various diseases such as cancer, neurodegenerative disorders, and diabetes, comprehending the post-translational modification of Keap1 not only deepens our understanding of Nrf2 signaling regulation but also contributes to the identification of novel drug targets and biomarkers. Consequently, this knowledge holds immense importance in the prevention and treatment of diseases induced by oxidative stress. Show less