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Articles by Ron Bose
HER2; p53 co-mutated cancers show increased histone acetylation and are sensitive to neratinib plus trastuzumab deruxtecan
Abstract In metastatic breast cancer, HER2-activating mutations often co-occur with TP53 mutations, a combination linked to poor response to neratinib and worse prognosis. To model this clinical challenge, we bred HER2V777L transgenic mice with two TP53 mutant alleles: TP53R172H (the murine homolog of human TP53 R175H) and TP53fl/fl, which mimics p53 truncations common in human tumors. TP53 mutations accelerated tumor development and reduced survival in HER2-mutant mice.
The TROP2 targeting antibody-drug conjugate IMMU-132 enhances the efficacy of radiation therapy for lung cancer
Abstract Studies suggest that the human trophoblast cell-surface antigen (TROP2) is highly expressed in most lung cancers and is associated with poor prognosis. Currently, there are no TROP2-directed ADCs approved for the treatment of lung cancer patients. IMMU-132 ADC (Sacituzumab govitecan) is a TROP-2-directed ADC recently approved for metastatic triple-negative breast cancer and urothelial cancer. However, its role in non-small cell carcinoma (NSCLC) has not been explored.
Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial | Nature Communications
Abstract CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774).
MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors | Journal of Clinical Oncology
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. HER2 mutations (n = 263), or HER2 mutations alone (n = 83) had been treated.
Breast Cancer, HER2 Mutations, and Overcoming Drug Resistance
A recent study suggests that HER2-mutated breast cancer may develop resistance to drugs that inhibit the tyrosine kinase domain of HER2 through developing mutations in HER3, which enhance the dimerization between HER2 and HER3. The HER3 mutations augment signaling. This study supports a specific approach to overcoming mutant-HER3–mediated resistance. Funding and Disclosures Disclosure forms provided by the authors are available at NEJM.org.
Genomic Characterization of Primary Invasive Lobular Breast Cancer
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Results Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples.
By Debora Fumagalli, David Brown, Peter Van Loo, Roberto Salgado, Christine Galant, François Bertucci, Peter Campbell, Gabriele Zoppoli, Gunes Gundem, Giancarlo Pruneri, Denis Larsimont, Marco Fornili, Françoise Rothé, Delphine Vincent, Naima Kheddoumi, Ghizlane Rouas, Samira Majjaj, Sylvain Brohée, Patrick Maisonneuve, Thomas Van Brussel, Diether Lambrechts, Ron Bose, Otto Metzger, Martine Piccart-Gebhart, Giuseppe Viale, Elia Biganzoli
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Journal of Clinical Oncology
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