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Article ; Online: Palbociclib plus letrozole induces a complete metabolic response in metastatic breast cancer patient with idiopathic thrombocytopenia.

Barberi, Vittoria / Renna, Davide / Annovazzi, Alessio / Ferretti, Gianluigi / Russillo, Michelangelo / Cognetti, Francesco

Recenti progressi in medicina

2022 Volume 113, Issue 6, Page(s) 376–379

Abstract: Breast cancer is still the leading cause of cancer-related deaths among women aged 20-59 and metastatic breast cancer remains an incurable disease. The therapeutic paradigm of patients with HR-positive HER2-negative metastatic breast cancer has been ... ...

Abstract	Breast cancer is still the leading cause of cancer-related deaths among women aged 20-59 and metastatic breast cancer remains an incurable disease. The therapeutic paradigm of patients with HR-positive HER2-negative metastatic breast cancer has been expanded by the introduction of the inhibitors of cyclin-dependent kinases 4/6. Three compounds, palbociclib, ribociclib, and abemaciclib, have already been approved by the Food and Drug Administration (FDA) for use together with endocrine therapy; abemaciclib is also approved as a single agent. In the first-line setting, all three agents - together with an aromatase inhibitor (AI) - substantially prolonged progression-free survival. Hematologic toxicities are the most common adverse events associated with CDK4/6i, mainly with palbociclib and ribociclib. Due to the hematologic toxicity, the prescribing information of palbociclib (P) recommends monitoring complete blood counts before starting therapy and at the beginning of each cycle, as well as on day 15 of the first 2 cycles. However, there are no guidelines regarding the management of patients candidate to CDK4/6i who have bone marrow impairment. Neutropenia frequently occurs during the treatment with P, whereas thrombocytopenia represents a rare event. We here report a case of a 60-year-old woman with idiopathic thrombocytopenia treated with P plus letrozole, who presented a metabolic complete response.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Breast Neoplasms/complications ; Breast Neoplasms/drug therapy ; Female ; Humans ; Letrozole/therapeutic use ; Middle Aged ; Piperazines ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pyridines ; Thrombocytopenia/chemically induced ; Thrombocytopenia/drug therapy
Chemical Substances	Piperazines ; Protein Kinase Inhibitors ; Pyridines ; Letrozole (7LKK855W8I) ; palbociclib (G9ZF61LE7G)
Language	English
Publishing date	2022-06-25
Publishing country	Italy
Document type	Case Reports ; Journal Article
ZDB-ID	138266-4
ISSN	2038-1840 ; 0034-1193
ISSN (online)	2038-1840
ISSN	0034-1193
DOI	10.1701/3827.38111
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Article: Prognostic value of [18F]-FDG PET/CT in patients with meta-static breast cancer treated with cyclin-dependent inhibitors.

Annovazzi, Alessio / Rea, Sandra / Maccora, Daria / Pizzuti, Laura / Ferretti, Gianluigi / Vici, Patrizia / Cappuzzo, Federico / Sciuto, Rosa

Frontiers in oncology

2023 Volume 13, Page(s) 1193174

Abstract: Objective: The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy impressively improved the outcome of patients with hormone receptor-positive metastatic breast cancer. Despite their great efficacy, not all patients ... ...

Abstract	Objective: The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy impressively improved the outcome of patients with hormone receptor-positive metastatic breast cancer. Despite their great efficacy, not all patients respond to treatment and many of them develop acquired resistance. The aim of this retrospective study was to assess the role of [18F]-FDG PET/CT in predicting PFS and OS in breast cancer patients treated with CDK4/6i. Methods: 114 patients who performed an [18F]-FDG PET/CT scan before (PET1) and 2-6 months (PET2) after starting treatment were retrospectively enrolled. Metabolic response was evaluated by EORTC, PERCIST and Deauville Score and correlated to PFS and OS. Results: In patients who did not progress at PET2 (n = 90), PFS rates were not significantly different between classes of response by EORTC and PERCIST. Conversely, patients showing a Deauville score ≤3 had a longer PFS (median PFS 42 vs 21.0 months; p = 0.008). A higher total metabolic tumor volume at PET1 (TMTV1) was also associated with a shorter PFS (median 18 vs 42 months; p = 0.0026). TMTV1 and Deauville score were the only independent prognostic factors for PFS at multivariate analysis and their combination stratified the population in four definite classes of relapse risk. Conversely, the above parameters did not affect OS which was only influenced by a progressive metabolic disease at PET2 (3-years survival rate 29.8 vs 84.9%; p<0.0001). Conclusion: TMTV and metabolic response by Deauville score were significant prognostic factors for PFS in patients with breast cancer treated with CDK4/6i. Their determination could help physicians to select patients who may need a closer follow up.
Language	English
Publishing date	2023-07-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1193174
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Article: Second-Degree Type 2 Atrioventricular Block Requiring Permanent Cardiac Pacing in Patients on CDK4/6 Inhibitors: Report of Two Cases.

Cicini, Maria Paola / Ferretti, Gianluigi / Morace, Nicola / Nisticò, Cecilia / Cognetti, Francesco / Rulli, Francesco

Breast care (Basel, Switzerland)

2021 Volume 17, Issue 3, Page(s) 330–335

Abstract: Introduction: A wide spectrum of cardiovascular (CV) toxicity is associated with anticancer treatment, and nearly all chemotherapeutic agents can elicit CV toxicity. Inhibitors of cyclin-dependent kinases 4/6 (CDK4/6Is) have become standard of care in ... ...

Abstract	Introduction: A wide spectrum of cardiovascular (CV) toxicity is associated with anticancer treatment, and nearly all chemotherapeutic agents can elicit CV toxicity. Inhibitors of cyclin-dependent kinases 4/6 (CDK4/6Is) have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC). CV side effects are uncommon with CDK4/6Is and only include QT prolongation, with a low incidence rate. Case presentation: This paper describes 2 cases of new-onset second-degree type 2 atrioventricular (AV) blocks requiring permanent cardiac pacing involving 2 women with MBC receiving ribociclib or abemaciclib. Both our patients had no known history or risk factors of cardiac disease and a normal 12-lead resting electrocardiogram (ECG) when diagnosed with breast adenocarcinoma. Both patients have been subjected to surveillance for cardiotoxicity with serial ECG and echocardiography. No left ventricular dysfunction or arrhythmia was found during the follow-up, and cardiac biomarkers were normal. Conclusion: To our knowledge, these are the first cases reported in the literature of new-onset advanced AV blocks in patients under treatment with CDK4/6Is, suggesting the clinical relevance of a more frequent ECG monitoring, besides the QT interval, in these patients.
Language	English
Publishing date	2021-11-12
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2202236-3
ISSN	1661-3805 ; 1661-3791
ISSN (online)	1661-3805
ISSN	1661-3791
DOI	10.1159/000519728
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Article: Progesterone, progestins, pregnancy and breast cancer risk.

Ferretti, Gianluigi

Breast cancer research and treatment

2007 Volume 103, Issue 3, Page(s) 373–374

MeSH term(s)	Breast Neoplasms/diagnosis ; Breast Neoplasms/etiology ; Breast Neoplasms/metabolism ; Cell Proliferation ; Clinical Trials as Topic ; Estrogen Replacement Therapy/adverse effects ; Female ; Hormone Replacement Therapy/adverse effects ; Humans ; Pregnancy ; Progesterone/metabolism ; Progestins/metabolism ; Recurrence ; Risk ; Risk Factors
Chemical Substances	Progestins ; Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2007-07
Publishing country	Netherlands
Document type	Letter
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-006-9379-5
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Zs.A 1655: Show issues

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Article ; Online: Temsirolimus for advanced renal-cell carcinoma.

Ferretti, Gianluigi

The New England journal of medicine

2007 Volume 357, Issue 10, Page(s) 1050; author reply 1050–1

MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/mortality ; Carcinoma, Renal Cell/secondary ; Humans ; Interferon-alpha/therapeutic use ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/mortality ; Research Design ; Sirolimus/analogs & derivatives ; Sirolimus/therapeutic use ; Survival Analysis
Chemical Substances	Interferon-alpha ; temsirolimus (624KN6GM2T) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2007-09-06
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
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Article: Tumor Microenvironment: Implications in Melanoma Resistance to Targeted Therapy and Immunotherapy.

Falcone, Italia / Conciatori, Fabiana / Bazzichetto, Chiara / Ferretti, Gianluigi / Cognetti, Francesco / Ciuffreda, Ludovica / Milella, Michele

Cancers

2020 Volume 12, Issue 10

Abstract: Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved ... ...

Abstract	Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase (MEK), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.
Language	English
Publishing date	2020-10-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12102870
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Article ; Online: Forkhead box P3-positive regulatory T cells as therapeutic target for breast cancer.

Ferretti, Gianluigi

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2007 Volume 25, Issue 23, Page(s) e29; author reply e30

MeSH term(s)	Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/metabolism ; Forkhead Transcription Factors/biosynthesis ; Humans ; Interleukin-2 Receptor alpha Subunit/biosynthesis ; Leukocyte Common Antigens/biosynthesis ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Phenotype ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/physiology
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors ; Interleukin-2 Receptor alpha Subunit ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2007-08-10
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2006.10.3374
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Colorectal cancer stem cells properties and features: evidence of interleukin-8 involvement.

Conciatori, Fabiana / Bazzichetto, Chiara / Falcone, Italia / Ferretti, Gianluigi / Cognetti, Francesco / Milella, Michele / Ciuffreda, Ludovica

Cancer drug resistance (Alhambra, Calif.)

2019 Volume 2, Issue 4, Page(s) 968–979

Abstract: Colorectal cancer (CRC) still remains a disease with high percentage of death, principally due to therapy resistance and metastasis. During the time the hypothesis has been reinforced that CRC stem cells (CRCSC) are involved in allowing intratumoral ... ...

Abstract	Colorectal cancer (CRC) still remains a disease with high percentage of death, principally due to therapy resistance and metastasis. During the time the hypothesis has been reinforced that CRC stem cells (CRCSC) are involved in allowing intratumoral heterogeneity, drug escape mechanisms and secondary tumors. CRCSC are characterized by specific surface markers (i.e., CD44 and CD133), signaling pathways activation (i.e., Wnt and Notch) and gene expression (i.e., Oct4 and Snail), which confer to CRCSC self-renewal abilities and pluripotent capacity. Interleukin (IL)-8 is correlated to CRC progression, development of liver metastases and chemoresistance; moreover, IL-8 modulates not only stemness maintenance but also stemness promotion, such as epithelial-mesenchymal transition. This review wants to give a brief and up-to-date overview on IL-8 implication in CRCSC cues.
Language	English
Publishing date	2019-12-19
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2578-532X
ISSN (online)	2578-532X
DOI	10.20517/cdr.2019.56
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Article: Fibroblast-Induced Paradoxical PI3K Pathway Activation in PTEN-Competent Colorectal Cancer: Implications for Therapeutic PI3K/mTOR Inhibition.

Conciatori, Fabiana / Salvati, Erica / Ciuffreda, Ludovica / Shirasawa, Senji / Falcone, Italia / Cognetti, Francesco / Ferretti, Gianluigi / Zeuli, Massimo / Del Bufalo, Donatella / Bazzichetto, Chiara / Milella, Michele

Frontiers in oncology

2022 Volume 12, Page(s) 862806

Abstract: Purpose: Tumor-microenvironment interactions are important determinants of drug resistance in colorectal cancer (CRC). We, therefore, set out to understand how interactions between genetically characterized CRC cells and stromal fibroblasts might ... ...

Abstract	Purpose: Tumor-microenvironment interactions are important determinants of drug resistance in colorectal cancer (CRC). We, therefore, set out to understand how interactions between genetically characterized CRC cells and stromal fibroblasts might influence response to molecularly targeted inhibitors. Techniques: Sensitivity to PI3K/AKT/mTOR pathway inhibitors of CRC cell lines, with known genetic background, was investigated under different culture conditions [serum-free medium, fibroblasts' conditioned medium (CM), direct co-culture]. Molecular pathway activation was monitored using Western Blot analysis. Immunoprecipitation was used to detect specific mTOR complex activation. Immunofluorescence was used to analyze cellular PTEN distribution, while different mutant PTEN plasmids were used to map the observed function to specific PTEN protein domains. Results: Exposure to fibroblast-CM resulted in increased growth-inhibitory response to double PI3K/mTOR inhibitors in PTEN-competent CRC cell lines harboring Data interpretation: Microenvironmental cues, in particular soluble factors produced by stromal fibroblasts, profoundly influence PI3K pathway signaling and functional response to specific inhibitors in CRC cells, depending on their mutational background and PTEN status.
Language	English
Publishing date	2022-06-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.862806
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Article ; Online: PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy.

Conciatori, Fabiana / Bazzichetto, Chiara / Falcone, Italia / Ciuffreda, Ludovica / Ferretti, Gianluigi / Vari, Sabrina / Ferraresi, Virginia / Cognetti, Francesco / Milella, Michele

International journal of molecular sciences

2020 Volume 21, Issue 15

Abstract: Mounting preclinical and clinical evidence indicates that rewiring the host immune system in favor of an antitumor microenvironment achieves remarkable clinical efficacy in the treatment of many hematological and solid cancer patients. Nevertheless, ... ...

Abstract	Mounting preclinical and clinical evidence indicates that rewiring the host immune system in favor of an antitumor microenvironment achieves remarkable clinical efficacy in the treatment of many hematological and solid cancer patients. Nevertheless, despite the promising development of many new and interesting therapeutic strategies, many of these still fail from a clinical point of view, probably due to the lack of prognostic and predictive biomarkers. In that respect, several data shed new light on the role of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) in affecting the composition and function of the tumor microenvironment (TME) as well as resistance/sensitivity to immunotherapy. In this review, we summarize current knowledge on PTEN functions in different TME compartments (immune and stromal cells) and how they can modulate sensitivity/resistance to different immunological manipulations and ultimately influence clinical response to cancer immunotherapy.
MeSH term(s)	Humans ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; PTEN Phosphohydrolase/immunology ; Tumor Microenvironment/immunology
Chemical Substances	PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2020-07-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21155337
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