Browsing by Author "Bravo, María Loreto"

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    Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients
    (MDPI, 2023) Pinto, Mauricio P.; Bravo, María Loreto; Córdova Delgado, Miguel; Hill, Charlotte N.; Muñoz Medel, Matías; Retamal, Ignacio N.; Fernández, M. Fernanda; Sánchez, Carolina; Sáez, Mauricio A.; Morales Pison, Sebastián; García Bloj, Benjamín; Garrido, Marcelo; Latapiat, Verónica; Martín, Alberto J.M.; Fernández Ramírez, Ricardo; Owen Gareth Ivor
    Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3? massive analysis of cDNA ends (3?MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-?-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/?-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients.
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    Palbociclib in advanced stage hormone receptor-positive breast cancer: real- world data from a Chilean multicentre registry
    (2023) Walbaum García, Benjamín Vicente; Reyes, José Miguel ; Rodríguez, Pablo ; Muñiz Muñoz, María Sabrina; Medina Araya, Lidia Marjorie; Ibáñez Cáceres, Carolina; Merino Lara, Tomás Rodrigo; Pinto, Mauricio ; Bravo, María Loreto ; Acevedo Claros, Francisco Nicolás; Bennett Laso, José Tomás; Sánchez Rojel, César Giovanni
    Background The addition of cyclin-dependent kinases inhibitors (CDKi) to endocrine therapy (ET) as the first- or second line treatment improves progression-free and overall survival (OS) in hormone receptor-positive, HER2 negative (HR+/HER2-) advanced stage breast cancer (ABC). Our study compared survival rates and prognostic factors in Chilean patients that used palbociclib as first or subsequent (≥second) lines of treatment in a real-world setting.Methods Our retrospective population-cohort study included HR+/HER2- ABC patients. We calculated 5-year OS and performed a multivariate analysis to determine prognostic factors.Results A total of 106 patients were included. Median age was 49 years (19–86), 28.3% (30) had de novo stage IV disease; 63% received palbociclib with ET as first line, 54% of them with aromatase inhibitor over fulvestrant. Median OS for the entire cohort was 99 months and 5-year OS was 69%. Patients that received first line palbociclib had a 5-year OS of 89% versus 43% for ET monotherapy or ≥second line palbociclib (p = 0.0062). Multivariate analysis showed that the year at diagnosis and CDKi timing (first line versus ≥second line) were significantly associated with OS.Conclusion Our real-world data show that first-line CDKi + ET provides a statistically significant benefit in OS versus ≥second line in HR+/HER2- ABC patients.