Neoadjuvant therapy for triple-negative breast cancer: potential predictive biomarkers of activity and efficacy of platinum chemotherapy, PARP- and immune-checkpoint-inhibitors.

Neoadjuvant therapy for triple-negative breast cancer: potential predictive biomarkers of activity and efficacy of platinum chemotherapy, PARP- and immune-checkpoint-inhibitors. Expert Opin Pharmacother. 2020 Feb 13;:1-13 Authors: Garufi G, Palazzo A, Paris I, Orlandi A, Cassano A, Tortora G, Scambia G, Bria E, Carbognin L Abstract Introduction: Despite recent advances in the molecular characterization of triple-negative breast cancer (TNBC), the standard treatment for early-stage TNBC is represented by the historically used anthracycline and taxane-based chemotherapy. In this modern era of precision medicine, several new therapeutic strategies and novel agents have been investigated in the neoadjuvant setting of TNBC, in order to individualize treatment.Areas covered: This review provides a comprehensive overview of the currently available evidence regarding the activity and efficacy of platinum agents, PARP- and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, highlighting the available data on potential predictive biomarkers of response or resistance to such treatments.Expert opinion: The genomic and immune landscape of TNBC has encouraged the exploration of drugs that interfere with the DNA repair mechanism and that modulate immune response. Overall, these drugs seem to improve the pCR rate in TNBC, despite preliminary and heterogeneous results. Taking into account the economic issues and the side effects of these drugs, it is cruci...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

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RARITAN, N.J., February 3, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today multiple data presentations from a robust solid tumor portfolio that will be featured at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, taking place February 13-15 in San Francisco. Company-sponsored data presentations will include clinical results for ERLEADA® (apalutamide) and niraparib in prostate cancer; and BALVERSA™ (erdafitinib) in bladder cancer. “We are committed to improving outcomes in patients with prostate and bladder cancer where high unmet ...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
CONCLUSION: These results suggest that genomic disturbances in BRCA-related DNA repair mechanisms, reflected by a dominant mutational signature 3, confer increased chemotherapy sensitivity. Cancers that survive neoadjuvant chemotherapy, frequently have alterations in cell cycle regulating genes but different genes of the same pathways are affected in different patients. PMID: 31919134 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Authors: Hartkopf AD, Müller V, Wöckel A, Lux MP, Janni W, Ettl J, Belleville E, Schütz F, Fasching PA, Kolberg HC, Welslau M, Overkamp F, Taran FA, Brucker SY, Wallwiener M, Tesch H, Fehm TN, Schneeweiss A, Lüftner D Abstract In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between ef...
Source: Geburtshilfe und Frauenheilkunde - Category: OBGYN Tags: Geburtshilfe Frauenheilkd Source Type: research
Authors: Takeshita T, Asaoka M, Katsuta E, Photiadis SJ, Narayanan S, Yan L, Takabe K Abstract Polo-like kinase 1 (PLK1), the most investigated member of the PLK family, plays a pivotal role both in the p53-mediated regulation of DNA damage repair and in mitosis, especially in the G2/M phase. However, the evidence on the clinical and prognostic relevance of PLK1 is limited to triple negative subtype among breast cancer (BC). We hypothesized that high expression of PLK1 is associated with TP53 inactivation, DNA repair deficiency, and worse prognosis in ER positive in BC in a large-scale cohort should clarify its cli...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
inivasan Madhusudan Genomic instability could be a beneficial predictor for anthracycline or taxane chemotherapy. We interrogated 188 DNA repair genes in the METABRIC cohort (n = 1980) to identify genes that influence overall survival (OS). We then evaluated the clinicopathological significance of ERCC1 in early stage breast cancer (BC) (mRNA expression (n = 4640) and protein level, n = 1650 (test set), and n = 252 (validation)) and in locally advanced BC (LABC) (mRNA expression, test set (n = 2340) and validation (TOP clinical trial cohort, n = 120); and protein level (n = 120)). In the multivariate model, ERCC1 was i...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was carried out in accordance with the recommendations of international guidelines and ethical standards with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Ethics Committee of Kunming General Hospital, China. miRNAs, Plasmids, Transfection, and Irradiation To predict miRNAs with potential binding sites in the 3′UTR of PHLDA2, Targetscan (http://www.targetscan.org/), miRanda (http://www.microrna.org/), and Diana database (http://diana.cslab,ece.nura.gr/) algorithms were u...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: High mast cell gene expression is associated with lower pCR rate. TIL counts and most immune parameters decrease after neoadjuvant chemotherapy.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Abstract The aim of the study was to understand the role of homologous recombination repair (HRR) pathway genes in development of chemotolerance in breast cancer (BC). For this purpose, chemotolerant BC cells were developed in MCF-7 and MDA MB 231 cell lines after treatment with two anthracycline anti-tumor antibiotics doxorubicin and nogalamycin at different concentrations for 48 h with differential cell viability. The drugs were more effective in MCF-7 (IC50: 0.214-0.242 µM) than in MDA MB 231 (IC50: 0.346-0.37 µM) as shown by cell viability assay. The drugs could reduce the protein ex...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research
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