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1. Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, De Luca, Francesca, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Di Leo, Angelo, and Malorni, Luca

Published
2021
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2. Targeting the CDK4/6 Pathway in Breast Cancer

Author

Malorni, Luca, Migliaccio, Ilenia, Guarducci, Cristina, Bonechi, Martina, Di Leo, Angelo, Veronesi, Umberto, editor, Goldhirsch, Aron, editor, Veronesi, Paolo, editor, Gentilini, Oreste Davide, editor, and Leonardi, Maria Cristina, editor

Published
2017
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3. Supplemental Figure 1 from TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer

Author

Jeselsohn, Rinath, primary, Barry, William T., primary, Migliaccio, Ilenia, primary, Biagioni, Chiara, primary, Zhao, Jin, primary, De Tribolet-Hardy, Jonas, primary, Guarducci, Cristina, primary, Bonechi, Martina, primary, Laing, Naomi, primary, Winer, Eric P., primary, Brown, Myles, primary, Leo, Angelo Di, primary, and Malorni, Luca, primary

Published
2023
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6. Additional file 5 of Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, Luca, Francesca De, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Abstract

Additional file 5: Figure S5. RB1 and GAPDH gene expression analysis. A) distribution of GAPDH and RB1 copies number in single CTCs, B) distribution of mean number of copies of GAPDH and RB1 (tot n copies/n cells).

Published
2021
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7. Additional file 6 of Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, Luca, Francesca De, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Abstract

Additional file 6: Figure S6. Mean number of copies of GAPDH and RB1 broken into timepoint.

Published
2021
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8. Additional file 3 of Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, Luca, Francesca De, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Subjects
food and beverages, eye diseases
Abstract

Additional file 3: Figure S3. Cell lines set up of ddPCR assay. A) RB1 expression on PDS and PDR cell lines confirm the reduction of RB1 expression among PDS and PDS cell lines, *** p

Published
2021
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9. Additional file 1 of Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, Luca, Francesca De, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Abstract

Additional file 1: Figure S1. CTCs dynamics. Spider plot of CTC dynamics for each timepoint colored according to CB.

Published
2021
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10. Additional file 2 of Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, Luca, Francesca De, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Abstract

Additional file 2: Figure S2. T47D set up of ddPCR assay. A, B-2D plot of T47D PDS and PDR, C, D- concentration plot of T47D PDS and PDR; PDS: sensitive to palbociclib, PDR resistant to palbociclib.

Published
2021
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11. Additional file 4 of Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial

Author

Galardi, Francesca, Luca, Francesca De, Biagioni, Chiara, Migliaccio, Ilenia, Curigliano, Giuseppe, Minisini, Alessandro M., Bonechi, Martina, Moretti, Erica, Risi, Emanuela, McCartney, Amelia, Benelli, Matteo, Romagnoli, Dario, Cappadona, Silvia, Gabellini, Stefano, Guarducci, Cristina, Conti, Valerio, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Abstract

Additional file 4: Figure S4. Images of a patient sample CTCs. Images of CTCs identified by A) Cell Search system, B) DEP array. C) 2-D plot RB1- droplets positive for Rb1 expression, GAPDH- droplets positive for GAPDH; RB1+ GAPDH- droplets positive for both RB1 and GAPDH.

Published
2021
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13. Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial

Author

McCartney, Amelia, primary, Bonechi, Martina, additional, De Luca, Francesca, additional, Biagioni, Chiara, additional, Curigliano, Giuseppe, additional, Moretti, Erica, additional, Minisini, Alessandro Marco, additional, Bergqvist, Mattias, additional, Benelli, Matteo, additional, Migliaccio, Ilenia, additional, Galardi, Francesca, additional, Risi, Emanuela, additional, De Santo, Irene, additional, Romagnoli, Dario, additional, Biganzoli, Laura, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2020
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14. Glucose Metabolic Reprogramming of ER Breast Cancer in Acquired Resistance to the CDK4/6 Inhibitor Palbociclib+

Author

Lorito, Nicla, primary, Bacci, Marina, additional, Smiriglia, Alfredo, additional, Mannelli, Michele, additional, Parri, Matteo, additional, Comito, Giuseppina, additional, Ippolito, Luigi, additional, Giannoni, Elisa, additional, Bonechi, Martina, additional, Benelli, Matteo, additional, Migliaccio, Ilenia, additional, Malorni, Luca, additional, Chiarugi, Paola, additional, and Morandi, Andrea, additional

Published
2020
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15. Abstract P5-06-11: Serum thymidine kinase-1 activity (TKa) as a prognostic marker in premenopausal women with hormone receptor positive (HR+) operable breast cancer (BC)

Author

Malorni, Luca, primary, Migliaccio, Ilenia, additional, Biagioni, Chiara, additional, Rossi, Lorenzo, additional, De Santo, Irene, additional, Love, Richard L, additional, McCartney, Amelia, additional, Bergqvist, Mattias, additional, Bonechi, Martina, additional, De Luca, Francesca, additional, Galardi, Francesca, additional, Benelli, Matteo, additional, Romagnoli, Dario, additional, Risi, Emanuela, additional, Biganzoli, Laura, additional, Laudico, Adriano, additional, Van Dinh, Nguyen, additional, and Leo, Angelo Di, additional

Published
2020
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17. suppl_table_1_rev – Supplemental material for An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06)

Author

Risi, Emanuela, Biagioni, Chiara, Benelli, Matteo, Migliaccio, Ilenia, McCartney, Amelia, Bonechi, Martina, Guarducci, Cristina, Hilbers, Florentine, Cosimo, Serena Di, Huober, Jens, Romagnoli, Dario, Boccalini, Giulia, Vitale, Stefania, Sotiriou, Christos, Biganzoli, Laura, Leo, Angelo Di, and Malorni, Luca

Subjects
110203 Respiratory Diseases, FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental material, suppl_table_1_rev for An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06) by Emanuela Risi, Chiara Biagioni, Matteo Benelli, Ilenia Migliaccio, Amelia McCartney, Martina Bonechi, Cristina Guarducci, Florentine Hilbers, Serena Di Cosimo, Jens Huober, Dario Romagnoli, Giulia Boccalini, Stefania Vitale, Christos Sotiriou, Laura Biganzoli, Angelo Di Leo and Luca Malorni in Therapeutic Advances in Medical Oncology

Published
2019
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18. Prognostic role of serum thymidine kinase 1 activity in patients with hormone receptor–positive metastatic breast cancer: Analysis of the randomised phase III Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT)

Author

McCartney, Amelia, Biagioni, Chiara, Schiavon, Gaia, Bergqvist, Mattias, Mattsson, Karin, Migliaccio, Ilenia, Benelli, Matteo, Romagnoli, Dario, Bonechi, Martina, Boccalini, Giulia, Pestrin, Marta, Galardi, Francesca, De Luca, Francesca, Biganzoli, Laura, Piccart-Gebhart, Martine, Gradishar, William W.J., Chia, Stephen, Di Leo, Angelo, Malorni, Luca, McCartney, Amelia, Biagioni, Chiara, Schiavon, Gaia, Bergqvist, Mattias, Mattsson, Karin, Migliaccio, Ilenia, Benelli, Matteo, Romagnoli, Dario, Bonechi, Martina, Boccalini, Giulia, Pestrin, Marta, Galardi, Francesca, De Luca, Francesca, Biganzoli, Laura, Piccart-Gebhart, Martine, Gradishar, William W.J., Chia, Stephen, Di Leo, Angelo, and Malorni, Luca

Abstract

Background: Thymidine kinase 1 (TK1) plays a critical role in DNA synthesis and cell proliferation. Recent studies have shown potential for serum TK1 activity (sTKa) as a prognostic marker and indicator of early response to endocrine therapy in advanced breast cancer. The aim of this study is to assess the correlation between sTKa and patient outcome. Patients and methods: The Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) was a double-blind, double-dummy, randomised trial of fulvestrant versus exemestane after progression on non-steroidal aromatase inhibitor therapy, in postmenopausal women with advanced breast cancer. Retrospective analyses of serum archived from EFECT were conducted. sTKa was assessed using the DiviTum® assay on samples collected at baseline, after three and six months of endocrine therapy, and at disease progression. Results: The median time to progression (mTTP) for patients with low baseline sTKa levels was 5.03 months (95% confidence interval [CI]: 3.91–5.89) versus 2.57 months (95% CI: 2.04–3.52) in patients with high sTKa baseline levels (P < 0.0001). On treatment, patients whose sTKa increased from baseline had a significantly shorter mTTP (3.39 months, 95% CI: 2.14–4.11) than those without an sTKa increase (5.39 months, 95% CI: 4.01–6.68) (P = 0.0045). Similar results were observed in the separate EFECT treatment arms. After adjusting for major prognostic factors, sTKa remained an independent marker. Conclusion: sTKa is a potential circulating prognostic marker in patients with advanced breast cancer treated with endocrine therapy. It may also represent a tool for upfront identification of endocrine therapy resistance and early positive response to therapy. Independent validation of these results is warranted., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Published
2019

19. An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06)

Author

Risi, Emanuela, Biagioni, Chiara, Benelli, Matteo, Migliaccio, Ilenia, McCartney, Amelia, Bonechi, Martina, Guarducci, Cristina, Hilbers, Florentine FS, Di Cosimo, Serena, Huober, J., Romagnoli, Dario, Boccalini, Giulia, Vitale, Stefania, Sotiriou, Christos, Biganzoli, Laura, Di Leo, A., Malorni, Luca, Risi, Emanuela, Biagioni, Chiara, Benelli, Matteo, Migliaccio, Ilenia, McCartney, Amelia, Bonechi, Martina, Guarducci, Cristina, Hilbers, Florentine FS, Di Cosimo, Serena, Huober, J., Romagnoli, Dario, Boccalini, Giulia, Vitale, Stefania, Sotiriou, Christos, Biganzoli, Laura, Di Leo, A., and Malorni, Luca

Abstract

Background: Chemotherapy added to anti-HER2 agents (H) is the treatment of choice in patients with HER2+ early breast cancer. However, HER2+ tumours are clinically and biologically heterogeneous, and treatment response varies significantly by hormone receptor (HR) status and molecular subtype. Predictive biomarkers are needed in this context. This study assessed whether an RB-1 loss of function gene signature (RBsig) is predictive of response to neoadjuvant chemotherapy in combination with trastuzumab, lapatinib or both, within the NeoALTTO trial. Methods: We collected RNA-sequencing data from pretreatment biopsies derived from the NeoALTTO trial. RBsig expression was computed retrospectively and correlated with pathological complete response (pCR) using receiver-operating characteristic (ROC) curves. The RBsig was dichotomised as High/Low in correspondence to the 25th percentile. Reported p values resulted from Fisher’s exact test. Results: Of 455 NeoALTTO patients, 244 were eligible for this substudy (HR+ n = 129; HR− n = 115). Overall, pCR rate was significantly higher in patients with RBsig High tumours than those with RBsig Low (35% versus 18% respectively; p = 0.01). The area under the ROC curve (AUC) was 0.60 (95% CI 0.52–0.67). A remarkably low pCR rate of 11% was seen in HR+/RBsig Low patients versus 28% in HR+/RBsig High. Conclusions: These results indicate RBsig may add valuable information to HER2 and HR expression, which may in turn inform treatment choices. HR+/HER2+/RBsig Low breast cancers exhibited the poorest pathological response following chemotherapy plus H. Accordingly, in such patients, endocrine therapy in combination with H and, possibly, a CDK4/6 inhibitor, may potentially prove to be a more effective treatment., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

20. Additional file 1 of ddSeeker: a tool for processing Bio-Rad ddSEQ single cell RNA-seq data

Author

Romagnoli, Dario, Boccalini, Giulia, Bonechi, Martina, Biagioni, Chiara, Fassan, Paola, Bertorelli, Roberto, Sanctis, Veronica, Leo, Angelo, Migliaccio, Ilenia, Malorni, Luca, and Benelli, Matteo

Abstract

Supplementary text, figures and tables. Supplementary text 1. Classification of error tags. Supplementary text 2. Detailed algorithm description. Supplementary figure 1. Linker alignment analysis. Supplementary figure 2. Error tags distribution for the in-house dataset. Supplementary table 1. Linker alignment analysis. Supplementary table 2. Error tags distribution for the Illumina dataset. Supplementary table 3. Error tags distribution for the in-house dataset. (PDF 407 kb)

Published
2018
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21. Mechanisms of Resistance to CDK4/6 Inhibitors: Potential Implications and Biomarkers for Clinical Practice

Author

McCartney, Amelia, primary, Migliaccio, Ilenia, additional, Bonechi, Martina, additional, Biagioni, Chiara, additional, Romagnoli, Dario, additional, De Luca, Francesca, additional, Galardi, Francesca, additional, Risi, Emanuela, additional, De Santo, Irene, additional, Benelli, Matteo, additional, Malorni, Luca, additional, and Di Leo, Angelo, additional

Published
2019
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22. Abstract 3012: Single-cell transcriptomic characterization of luminal breast cancer cell lines with acquired resistance to the CDK4/6 inhibitor palbociclib

Author

Benelli, Matteo, primary, Boccalini, Giulia, additional, Romagnoli, Dario, additional, Bonechi, Martina, additional, Biagioni, Chiara, additional, Schiff, Rachel, additional, Angelis, Carmine De, additional, Leo, Angelo Di, additional, Migliaccio, Ilenia, additional, and Malorni, Luca, additional

Published
2019
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23. Abstract 4416: Plasma thymidine kinase activity in patients with luminal metastatic breast cancer treated with Palbociclib within the phase II TREnd trial

Author

Malorni, Luca, primary, Biagioni, Chiara, additional, Luca, Francesca De, additional, Bonechi, Martina, additional, Curigliano, Giuseppe, additional, Minisini, Alessandro M., additional, Moretti, Erica, additional, Bergqvist, Mattias, additional, Mattsson, Karin, additional, Risi, Emanuela, additional, Migliaccio, Ilenia, additional, Vitale, Stefania, additional, Gabellini, Stefano, additional, McCartney, Amelia, additional, Santo, Irene De, additional, Galardi, Francesca, additional, Boccalini, Giulia, additional, Benelli, Matteo, additional, Rossi, Lorenzo, additional, Biganzoli, Laura, additional, and Leo, Angelo Di, additional

Published
2019
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24. Prognostic role of serum thymidine kinase 1 activity in patients with hormone receptor–positive metastatic breast cancer: Analysis of the randomised phase III Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT)

Author

McCartney, Amelia, primary, Biagioni, Chiara, additional, Schiavon, Gaia, additional, Bergqvist, Mattias, additional, Mattsson, Karin, additional, Migliaccio, Ilenia, additional, Benelli, Matteo, additional, Romagnoli, Dario, additional, Bonechi, Martina, additional, Boccalini, Giulia, additional, Pestrin, Marta, additional, Galardi, Francesca, additional, De Luca, Francesca, additional, Biganzoli, Laura, additional, Piccart, Martine, additional, Gradishar, William J., additional, Chia, Stephen, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2019
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25. An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06)

Author

Risi, Emanuela, primary, Biagioni, Chiara, additional, Benelli, Matteo, additional, Migliaccio, Ilenia, additional, McCartney, Amelia, additional, Bonechi, Martina, additional, Guarducci, Cristina, additional, Hilbers, Florentine, additional, Di Cosimo, Serena, additional, Huober, Jens, additional, Romagnoli, Dario, additional, Boccalini, Giulia, additional, Vitale, Stefania, additional, Sotiriou, Christos, additional, Biganzoli, Laura, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2019
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26. A RB-1 loss of function gene-signature (RBsig) as a tool to predict response to neoadjuvant chemotherapy (CT) plus anti-HER2 agents (H): A substudy of the NeoALTTO trial (BIG 1-06).

Author

Risi, Emanuela, primary, Biagioni, Chiara, additional, Benelli, Matteo, additional, Migliaccio, Ilenia, additional, McCartney, Amelia, additional, Bonechi, Martina, additional, Guarducci, Cristina, additional, Hilbers, Florentine, additional, Di Cosimo, Serena, additional, Baselga, Jose, additional, Romagnoli, Dario, additional, Boccalini, Giulia, additional, Vitale, Stefania, additional, Grilli, Andrea, additional, Bicciato, Silvio, additional, Sotiriou, Christos, additional, Biganzoli, Laura, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2018
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27. Role of serum thymidine kinase-1 (TK1) activity in patients (pts) with hormone receptor positive (HR+) advanced breast cancer (ABC) treated with endocrine therapy (ET) in the EFECT trial.

Author

Malorni, Luca, primary, Biagioni, Chiara, additional, McCartney, Amelia, additional, Schiavon, Gaia, additional, Bergqvist, Mattias, additional, Benelli, Matteo, additional, Migliaccio, Ilenia, additional, Biganzoli, Laura, additional, Bonechi, Martina, additional, Boccalini, Giulia, additional, Pestrin, Marta, additional, Galardi, Francesca, additional, De Luca, Francesca, additional, Piccart-Gebhart, Martine J., additional, Gradishar, William John, additional, Chia, Stephen K. L., additional, and Di Leo, Angelo, additional

Published
2018
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28. Plasma thymidine kinase-1 activity predicts outcome in patients with hormone receptor positive and HER2 negative metastatic breast cancer treated with endocrine therapy

Author

Bonechi, Martina, primary, Galardi, Francesca, additional, Biagioni, Chiara, additional, De Luca, Francesca, additional, Bergqvist, Mattias, additional, Neumüller, Magnus, additional, Guarducci, Cristina, additional, Boccalini, Giulia, additional, Gabellini, Stefano, additional, Migliaccio, Ilenia, additional, Di Leo, Angelo, additional, Pestrin, Marta, additional, and Malorni, Luca, additional

Published
2018
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29. A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients

Author

Risi, Emanuela, primary, Grilli, Andrea, additional, Migliaccio, Ilenia, additional, Biagioni, Chiara, additional, McCartney, Amelia, additional, Guarducci, Cristina, additional, Bonechi, Martina, additional, Benelli, Matteo, additional, Vitale, Stefania, additional, Biganzoli, Laura, additional, Bicciato, Silvio, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2018
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31. TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer

Author

Jeselsohn, Rinath, primary, Barry, William T., additional, Migliaccio, Ilenia, additional, Biagioni, Chiara, additional, Zhao, Jin, additional, De Tribolet-Hardy, Jonas, additional, Guarducci, Cristina, additional, Bonechi, Martina, additional, Laing, Naomi, additional, Winer, Eric P., additional, Brown, Myles, additional, Leo, Angelo Di, additional, and Malorni, Luca, additional

Published
2016
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32. A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer

Author

Malorni, Luca, primary, Piazza, Silvano, additional, Ciani, Yari, additional, Guarducci, Cristina, additional, Bonechi, Martina, additional, Biagioni, Chiara, additional, Hart, Christopher D., additional, Verardo, Roberto, additional, Leo, Angelo Di, additional, and Migliaccio, Ilenia, additional

Published
2016
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33. Abstract S1-01: TransCONFIRM: The correlative analysis of breast tumors from patients with advanced hormone receptor positive disease identifies a genetic signature associated with decreased benefit from single agent fulvestrant

Author

Jeselsohn, Rinath M, primary, Barry, William T, additional, Zhao, Jin, additional, Buchwalter, Gilles, additional, Guarducci, Cristina, additional, Migliaccio, Ilenia, additional, Biagioni, Chiara, additional, Bonechi, Martina, additional, Laing, Naomi, additional, Rukazenkov, Yuri, additional, Winer, Eric P, additional, Brown, Myles, additional, Di Leo, Angelo, additional, and Malorni, Luca, additional

Published
2015
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34. Cyclin E1 and Rb modulation as common events at time of resistance to palbociclib in hormone receptor-positive breast cancer

Author

Ilenia Migliaccio, Angelo Di Leo, Luca Malorni, Dario Romagnoli, Giulia Boccalini, Matteo Benelli, C. Kent Osborne, Carmine De Angelis, Martina Bonechi, Rachel Schiff, Roberto Verardo, Chiara Biagioni, Cristina Guarducci, Guarducci, Cristina, Bonechi, Martina, Benelli, Matteo, Biagioni, Chiara, Boccalini, Giulia, Romagnoli, Dario, Verardo, Roberto, Schiff, Rachel, Osborne, C Kent, De Angelis, Carmine, Di Leo, Angelo, Malorni, Luca, and Migliaccio, Ilenia

Subjects
0301 basic medicine, Cell, Cancer, Palbociclib, Biology, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, lcsh:RC254-282, Article, 3. Good health, 03 medical and health sciences, Cyclin E1, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Breast cancer, Oncology, Hormone receptor, 030220 oncology & carcinogenesis, Gene expression, medicine, Cancer research, Biomarker (medicine), Pharmacology (medical), Radiology, Nuclear Medicine and imaging
Abstract

CDK4/6 inhibitors represent a new treatment standard for hormone receptor-positive (HR+), HER2-negative advanced breast cancer (BC) patients. Although efficacious, resistance to these agents is universal. Here, we profiled a large panel of HR+ BC cell lines with conditioned resistance to the CDK4/6 inhibitor palbociclib, and analyzed cell cycle-related markers by gene expression profiles (GEP) and western blot (WB). GEP showed high molecular heterogeneity among the models, with E2F targets being significantly enriched both during treatment and at the time of resistance. By both WB and GEP, a common molecular feature at the time of palbociclib resistance was the concomitant overexpression of cyclin E1 and down-regulation of Rb. CCNE1 was the only significantly up-regulated gene among E2F targets at resistance with CCNE1 genomic amplification being observed in two resistant models. Rb was downregulated in all resistant models; a reduction of RB1 copy number was observed in three resistant cell lines. In silico analyses showed that CCNE1/RB1 ratio correlated with palbociclib IC50 in different datasets of both breast and non-breast cancer cell lines, performing better than CCNE1 or RB1 taken separately. Finally, the CCNE1/RB1 ratio was shown to be an adverse prognostic factor in patients with ER+ BC and to be able to discriminate palbociclib-sensitive versus resistant among patients enrolled in the NeoPalAna trial, a neoadjuvant trial testing palbociclib, performing better than CCNE1 or RB1 alone. Our data suggest that the CCNE1/RB1 ratio may be a viable biomarker of palbociclib resistance, warranting further clinical validation., Biomarkers: Prognostic indicator for resistance to cell cycle–targeted drug The expression levels of two genes involved in controlling the cell cycle offers a promising predictive indicator of whether women with hormone receptor–positive breast cancer are likely to develop resistance to the drug palbociclib. A team led by Luca Malorni and Ilenia Migliaccio from the Hospital of Prato, Italy, analyzed gene and protein profiles in a panel of breast cancer cell lines with differential sensitivity to palbociclib. The researchers found that, compared to palbociclib-sensitive cell lines, those that were drug-resistant tended to have elevated expression of one cell-cycle–related gene, called CCNE1, and reduced expression of another, called Rb. The ratio of CCNE1:Rb expression proved to be an accurate prognostic factor among patients enrolled in a clinical trial of palbociclib, performing better than either CCNE1 or Rb levels on their own.

Published
2018

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