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Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.
NPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
View Article and Find Full Text PDFUnraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial.
ESMO Open
January 2025
Uro-Gynecologic Oncology Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy. Electronic address:
Background: Ovarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring BRCA1/2 mutations. However, the variability in treatment responses suggests the need to investigate factors beyond BRCA1/2 mutations, such as DNA repair mechanisms and epigenetic alterations.
View Article and Find Full Text PDFAnti-IL-6R Ab tocilizumab to treat paraneoplastic inflammatory syndrome of solid cancers.
ESMO Open
January 2025
Department of Medicine and DRCI, Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France.
Background: Paraneoplastic inflammatory syndrome (PIS) with fever and biological inflammation is a rare but severe condition often caused by the systemic production of interleukin 6 (IL-6) by cancer cells. We report on the efficacy of tocilizumab, an anti-IL-6 receptor antibody, in 35 patients with severe PIS.
Patients And Methods: All 35 patients with solid cancers (sarcomas, lung carcinoma, and breast carcinoma) diagnosed with a PIS from 2019 to 2024 treated with tocilizumab were analyzed in this single-center study (health authorities' approval R201-004-478).
Survival analysis of the non-metastatic cohort of the Italian Association for Medical Oncology (AIOM) Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy (GARIBALDI).
ESMO Open
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AUSL-IRCCS Clinical Cancer Center of Reggio Emilia, Reggio Emilia, Italy.
Background: Non-metastatic pancreatic ductal adenocarcinoma (PDAC) presents a challenging scenario: the rarity of the disease, the limited number of completed prospective trials, and the shortcomings of comparability across series produce several controversial topics and unanswered questions. Guideline recommendations usually include all the different therapeutic options, de facto transferring to the multidisciplinary team the responsibility on the final decision. This secondary analysis of the GARIBALDI study was aimed to explore the correlation of center type, self-declared volume, and commitment with the overall survival (OS) in patients with non-metastatic PDAC.
View Article and Find Full Text PDFEthnic origin in cancer clinical trials: overrated or understated? A comprehensive analysis of cancer clinical trials leading to FDA and EMA approvals between 2020 and 2022.
ESMO Open
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Division of Oncology, Department of Medicine I, Medical University Vienna, Vienna, Austria. Electronic address:
Background: Ethnic diversity in cancer clinical trials is essential to ensure that therapeutic advances are equitable and broadly applicable in multicultural societies. Yet, missing consensus on the documentation of ethnic origin, partially based on the complexity of the terminology and fear of discrimination, leads to suboptimal patient management of minority populations. Additionally, eligibility criteria, such as stringent laboratory cut-offs, often fail to account for variations across ethnic groups, potentially excluding patients without evidence-based justification.
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