Roberta Caputo - Academia.edu (original) (raw)

Papers by Roberta Caputo

Research paper thumbnail of Ribociclib Plus Letrozole in Italian Male Patients with Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Case Studies of Phase 3b CompLEEment-1 Trial

DOAJ (DOAJ: Directory of Open Access Journals), Oct 1, 2022

Research paper thumbnail of LCZ 696, administered during doxorubicin, trastuzumab or pertuzumab treatment, prevents cardiotoxicity in our in vitro model

Annals of Oncology, Sep 1, 2017

The most common EAs in all grades during trials are: hyponatremia 62%, hypokalemia 40%, hypophosp... more The most common EAs in all grades during trials are: hyponatremia 62%, hypokalemia 40%, hypophosphatemia 32%, hypomagnesemia 17% and hypocalcemia 12%. Overall, grade 3/4 EAs occurred in 19% of cases. More specifically, grade 3/4 EAs were observed, as follow: hyponatremia 10%, hypophosphatemia 6%, hypokalemia 5%, hypomagnesemia 1%, hypermagnesemia 1%. Grade 3/4 EAs occurred during the dose-limiting toxicity window in 8.73% of cases. Overall, diarrhea was associated with hypomagnesemia in all grades (HR 1.78, 95% CI: 1.32-2.39, p < 0.001), with G3/G4 hypokalemia (HR 1.93, 95% CI: 1.09-3.43, p ¼ 0.02) and hyponatremia in all grades (HR 0.79, 95% CI: 0.67-0.93, p ¼ 0.006). Vomiting was also associated with hypomagnesemia in all grades (HR 1.45, 95% CI: 1.08-1.95, p ¼ 0.01) and G3/4 hypokalemia (HR 2.91, 95% CI: 1.62-5.23, p < 0.001). Baseline hypoalbuminemia, hyponatremia and female gender are associated with higher risk of developing other EAs during trial in the univariate analysis. Patients who developed G3/4 EAs during follow-up had a poorer median overall survival (OS) (26 weeks vs 37 weeks, HR ¼ 1.61; 95% CI: 1.37-1.90; p < 0.001). Conclusions: Baseline EAs are common in patients with advanced cancers participating in phase I trials. This is the first study to demonstrate the clinical significance of baseline hypoalbuminemia and hyponatremia, which are predictors of development of other EAs in phase 1 patients. G3/4 EAs are adverse prognostic factors of OS independent of serum albumin levels.

Research paper thumbnail of 199P Correlation of circulating tumor DNA (ctDNA) or thymidine kinase activity (TKa) dynamic patterns with tumor response in patients (pts) with hormone receptor (HR)+ human epidermal growth factor 2 (HER2)– advanced breast cancer (ABC) on ribociclib (RIB) + letrozole (LET) in BioItaLEE trial

Research paper thumbnail of 258P Immune checkpoint inhibitors addition to chemotherapy in older patients with metastatic triple-negative breast cancer: A systematic review and meta-analysis

Annals of Oncology, Sep 1, 2022

Research paper thumbnail of Enzastaurin inhibits tumours sensitive and resistant to anti-EGFR drugs

British Journal of Cancer, Jul 29, 2008

We investigated the antitumour effect and ability to overcome the resistance to anti-EGFR drugs o... more We investigated the antitumour effect and ability to overcome the resistance to anti-EGFR drugs of enzastaurin, an inhibitor of VEGFR-dependent PKCb signalling. Enzastaurin was evaluated alone and in combination with the EGFR inhibitor gefitinib, on growth and signalling protein expression in human cancer cells sensitive and resistant to anti-EGFR drugs, both in vitro and in nude mice. We demonstrated the marked inhibitory activity of enzastaurin against GEO colon and PC3 prostate cancer cells and their gefitinibresistant counterparts GEO-GR and PC3-GR, accompanied by inhibition of pAkt and its effector pp70S6K, pGSK3b and VEGF expression and secretion. Moreover, enzastaurin showed a cooperative effect with gefitinib in parental and in gefitinib-resistant cells. Remarkably, these results were confirmed in vivo, where enzastaurin showed antitumour activity and cooperativity with gefitinib in mice grafted with GEO and GEO-GR tumours, incrementing their median survival and inhibiting the aforesaid protein expression and secretion in tumour specimens. In conclusion, enzastaurin by interfering with signalling proteins implicated in EGFR drug resistance markedly cooperates with gefitinib in sensitive and gefitinib-resistant tumours, thus overcoming and reverting such resistance and providing a rational basis for its development in patients resistant to anti-EGFR drugs.

Research paper thumbnail of Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

International Journal of Molecular Sciences, Sep 3, 2020

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the m... more The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients' characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67-0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]).

Research paper thumbnail of Targeting Autophagy in Breast Cancer

International Journal of Molecular Sciences, Oct 22, 2020

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differ... more Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development. Autophagy is a highly conserved homeostatic process that can be activated in response to antineoplastic agents as a cytoprotective mechanism. Inhibition of autophagy could enhance tumor cell death by diverse anti-cancer therapies, representing an attractive approach to control mechanisms of drug resistance. In this manuscript, we present a review of autophagy focusing on its interplay with targeted drugs used for breast cancer treatment.

Research paper thumbnail of Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies

EClinicalMedicine, May 1, 2023

Research paper thumbnail of Combined targeted inhibition of Bcl-2, Bcl-xL, EGFR and Protein Kinase A Type I causes potent antitumor, apoptotic and antiangiogenic activity

Research paper thumbnail of Novel anticancer drugs TLR9 agonists interfere with EGFR signaling and potently synergies with EGFR inhibitors and with bevacizumab in wild type and cetuximab-resistant colon cancer xenografts

Novel anticancer drugs TLR9 agonists interfere with EGFR signaling and potently synergies with EG... more Novel anticancer drugs TLR9 agonists interfere with EGFR signaling and potently synergies with EGFR inhibitors and with bevacizumab in wild type and cetuximab-resistant colon cancer xenograft

Research paper thumbnail of Corrigendum to ‘Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)’

ESMO open, Apr 1, 2021

C. De Angelis, D. Bruzzese, A. Bernardo, E. Baldini, L. Leo, A. Fabi, T. Gamucci, P. De Placido, ... more C. De Angelis, D. Bruzzese, A. Bernardo, E. Baldini, L. Leo, A. Fabi, T. Gamucci, P. De Placido, F. Poggio, S. Russo, V. Forestieri, R. Lauria, I. De Santo, R. Caputo, D. Cianniello, A. Michelotti, L. Del Mastro, M. De Laurentiis, M. Giuliano, S. De Placido & G. Arpino Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples; Department of Public Health, University of Naples “Federico II”, Naples; Oncologia Medica, Fondazione S. Maugeri IRCCS, Pavia; Department of Oncology, S. Luca Hospital, Lucca; Unit of Oncology, A.O.R.N. dei Colli, Napoli, Naples; Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome; Medical Oncology Unit, ASL Frosinone, Frosinone; UO Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova; Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine; Breast Oncology Department, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Azienda Ospedaliera Universitaria Pisana, Ospedale Santa Chiara, Pisa; University of Genova, Dipartimento di Medicina Interna e Specialità Mediche (DIMI), Genova, Italy

Research paper thumbnail of 212P Real-world progression-free survival 2 with CDK4/6 inhibitors plus endocrine therapy and subsequent line: Results from the multicenter SISTER study

Research paper thumbnail of 236P Trastuzumab deruxtecan in Italian real-world experience: Updated analysis from DE-REAL study

Research paper thumbnail of 224P Clinical features and outcomes in HER2+ mBC patients treated with trastuzumab deruxtecan: A subgroup analysis of the De-REAL study

Research paper thumbnail of 105P CDK4/6 inhibitors in hormone receptor-positive, HER2-negative, locally advanced breast cancer (LABC): Biological and clinical activity, and post-surgical approaches

Research paper thumbnail of 267P AB-ITALY: The impact of drug-drug interaction on abemaciclib treatment in Italian real world experience

Research paper thumbnail of Taxane-based adjuvant therapy for early breast cancer (EBC): A meta-analysis of the predictive effect of ER and HER2 status

Journal of Clinical Oncology, 2010

e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improv... more e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improvement of disease-free-survival (DFS) and overall survival (OS) as compared to anthracycline-based regimens (De Laurentiis et al., JCO 2008). It has been questioned, however, that this average benefit may results from a markedly improved outcome for some subsets of patients, with others not receiving any advantage. To check this hypothesis, we performed a meta-analysis of the predictive effects both of HER2 and of ER status by pooling subsets data of the available randomized trials (RTs). The efficacy of taxane-based regimens in the subgroup of triple-negative (TN) pts was also evaluated. Methods: We searched the Pubmed database to identify randomized trials that compared taxane-based with non-taxane-based adjuvant chemotherapy regimens for EBC and reported efficacy data according to: HER2 or ER or the combination HER2/ER or the TN status. We also searched the proceedings of major international conferences to i...

Research paper thumbnail of Combined blockade of protein kinase A and bcl-2 by antisense strategy induces apoptosis and inhibits tumor growth and angiogenesis

Clinical cancer research : an official journal of the American Association for Cancer Research, 2001

Protein kinase A type I (PKAI) plays a key role in neoplastic transformation, conveys mitogenic s... more Protein kinase A type I (PKAI) plays a key role in neoplastic transformation, conveys mitogenic signals from different sources, and is overexpressed in the majority of human tumors. Inhibition of PKAI by different tools results in cancer-cell growth inhibition in vitro and in vivo. We and others have recently shown that a novel class of mixed-backbone oligonucleotides targeting the PKAI subunit RIalpha exhibits improved pharmacokinetic properties and antitumor activity accompanied by increased apoptosis in several human cancer types in vitro and in vivo. The role of bcl-2 in the control of apoptosis has been widely documented, and the inhibition of bcl-2 expression and function may have important therapeutic implications. In fact, oligonucleotides antisense bcl-2 have shown antitumor activity in animal models and have successfully completed early clinical trials. Recent studies have demonstrated a direct role of PKA in the regulation of the bcl-2-dependent apoptotic pathway. Therefo...

Research paper thumbnail of Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells

Clinical cancer research : an official journal of the American Association for Cancer Research, 2000

Angiogenesis plays a key role in tumor growth and metastasis. The transforming growth factor alph... more Angiogenesis plays a key role in tumor growth and metastasis. The transforming growth factor alpha (TGF-alpha)-epidermal growth factor receptor (EGFR) autocrine pathway controls in part the production of angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cancer cells. In this study, we have evaluated the antiangiogenic and antitumor activity of monoclonal antibody (MAb) C225, an anti-EGFR chimeric human-mouse MAb, alone and in combination with a human VEGF antisense (AS) 21-mer phosphorothioate oligonucleotide (VEGF-AS) in human GEO colon cancer cells. MAb C225 treatment determined a dose-dependent inhibition of VEGF, bFGF, and TGF-alpha production by GEO cells in vitro. Treatment with VEGF-AS caused a selective inhibition in VEGF expression by GEO cells in vitro. Treatment of immunodeficient mice bearing established, palpable GEO xenografts for 3 weeks with VEGF-AS or with MAb C225 determined a cytostatic reversible inh...

Research paper thumbnail of 8-Chloro-cyclic AMP inhibits autocrine and angiogenic growth factor production in human colorectal and breast cancer

Clinical cancer research : an official journal of the American Association for Cancer Research, 1997

8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protei... more 8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protein kinase A, a signaling protein directly involved in cell proliferation and neoplastic transformation, and that causes growth inhibition in a variety of human cancer cell types. In this report, we have investigated the effects of 8-Cl-cAMP on the expression of several growth factors in human colon (GEO and LS174T) and breast (MDA-MB468) cancer cell lines. 8-Cl-cAMP treatment caused in the three cancer cell lines a significant dose- and time-dependent inhibition in the expression of various endogenous autocrine growth factors, such as transforming growth factor alpha, amphiregulin, and CRIPTO, and of two angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor, at both the mRNA and protein levels. Furthermore, 8-Cl-cAMP treatment markedly inhibited the ability of all three cell lines to invade a basement membrane matrix in a chemoinvasion assay. Fi...

Research paper thumbnail of Ribociclib Plus Letrozole in Italian Male Patients with Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Case Studies of Phase 3b CompLEEment-1 Trial

DOAJ (DOAJ: Directory of Open Access Journals), Oct 1, 2022

Research paper thumbnail of LCZ 696, administered during doxorubicin, trastuzumab or pertuzumab treatment, prevents cardiotoxicity in our in vitro model

Annals of Oncology, Sep 1, 2017

The most common EAs in all grades during trials are: hyponatremia 62%, hypokalemia 40%, hypophosp... more The most common EAs in all grades during trials are: hyponatremia 62%, hypokalemia 40%, hypophosphatemia 32%, hypomagnesemia 17% and hypocalcemia 12%. Overall, grade 3/4 EAs occurred in 19% of cases. More specifically, grade 3/4 EAs were observed, as follow: hyponatremia 10%, hypophosphatemia 6%, hypokalemia 5%, hypomagnesemia 1%, hypermagnesemia 1%. Grade 3/4 EAs occurred during the dose-limiting toxicity window in 8.73% of cases. Overall, diarrhea was associated with hypomagnesemia in all grades (HR 1.78, 95% CI: 1.32-2.39, p < 0.001), with G3/G4 hypokalemia (HR 1.93, 95% CI: 1.09-3.43, p ¼ 0.02) and hyponatremia in all grades (HR 0.79, 95% CI: 0.67-0.93, p ¼ 0.006). Vomiting was also associated with hypomagnesemia in all grades (HR 1.45, 95% CI: 1.08-1.95, p ¼ 0.01) and G3/4 hypokalemia (HR 2.91, 95% CI: 1.62-5.23, p < 0.001). Baseline hypoalbuminemia, hyponatremia and female gender are associated with higher risk of developing other EAs during trial in the univariate analysis. Patients who developed G3/4 EAs during follow-up had a poorer median overall survival (OS) (26 weeks vs 37 weeks, HR ¼ 1.61; 95% CI: 1.37-1.90; p < 0.001). Conclusions: Baseline EAs are common in patients with advanced cancers participating in phase I trials. This is the first study to demonstrate the clinical significance of baseline hypoalbuminemia and hyponatremia, which are predictors of development of other EAs in phase 1 patients. G3/4 EAs are adverse prognostic factors of OS independent of serum albumin levels.

Research paper thumbnail of 199P Correlation of circulating tumor DNA (ctDNA) or thymidine kinase activity (TKa) dynamic patterns with tumor response in patients (pts) with hormone receptor (HR)+ human epidermal growth factor 2 (HER2)– advanced breast cancer (ABC) on ribociclib (RIB) + letrozole (LET) in BioItaLEE trial

Research paper thumbnail of 258P Immune checkpoint inhibitors addition to chemotherapy in older patients with metastatic triple-negative breast cancer: A systematic review and meta-analysis

Annals of Oncology, Sep 1, 2022

Research paper thumbnail of Enzastaurin inhibits tumours sensitive and resistant to anti-EGFR drugs

British Journal of Cancer, Jul 29, 2008

We investigated the antitumour effect and ability to overcome the resistance to anti-EGFR drugs o... more We investigated the antitumour effect and ability to overcome the resistance to anti-EGFR drugs of enzastaurin, an inhibitor of VEGFR-dependent PKCb signalling. Enzastaurin was evaluated alone and in combination with the EGFR inhibitor gefitinib, on growth and signalling protein expression in human cancer cells sensitive and resistant to anti-EGFR drugs, both in vitro and in nude mice. We demonstrated the marked inhibitory activity of enzastaurin against GEO colon and PC3 prostate cancer cells and their gefitinibresistant counterparts GEO-GR and PC3-GR, accompanied by inhibition of pAkt and its effector pp70S6K, pGSK3b and VEGF expression and secretion. Moreover, enzastaurin showed a cooperative effect with gefitinib in parental and in gefitinib-resistant cells. Remarkably, these results were confirmed in vivo, where enzastaurin showed antitumour activity and cooperativity with gefitinib in mice grafted with GEO and GEO-GR tumours, incrementing their median survival and inhibiting the aforesaid protein expression and secretion in tumour specimens. In conclusion, enzastaurin by interfering with signalling proteins implicated in EGFR drug resistance markedly cooperates with gefitinib in sensitive and gefitinib-resistant tumours, thus overcoming and reverting such resistance and providing a rational basis for its development in patients resistant to anti-EGFR drugs.

Research paper thumbnail of Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

International Journal of Molecular Sciences, Sep 3, 2020

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the m... more The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients' characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67-0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]).

Research paper thumbnail of Targeting Autophagy in Breast Cancer

International Journal of Molecular Sciences, Oct 22, 2020

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differ... more Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development. Autophagy is a highly conserved homeostatic process that can be activated in response to antineoplastic agents as a cytoprotective mechanism. Inhibition of autophagy could enhance tumor cell death by diverse anti-cancer therapies, representing an attractive approach to control mechanisms of drug resistance. In this manuscript, we present a review of autophagy focusing on its interplay with targeted drugs used for breast cancer treatment.

Research paper thumbnail of Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies

EClinicalMedicine, May 1, 2023

Research paper thumbnail of Combined targeted inhibition of Bcl-2, Bcl-xL, EGFR and Protein Kinase A Type I causes potent antitumor, apoptotic and antiangiogenic activity

Research paper thumbnail of Novel anticancer drugs TLR9 agonists interfere with EGFR signaling and potently synergies with EGFR inhibitors and with bevacizumab in wild type and cetuximab-resistant colon cancer xenografts

Novel anticancer drugs TLR9 agonists interfere with EGFR signaling and potently synergies with EG... more Novel anticancer drugs TLR9 agonists interfere with EGFR signaling and potently synergies with EGFR inhibitors and with bevacizumab in wild type and cetuximab-resistant colon cancer xenograft

Research paper thumbnail of Corrigendum to ‘Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI)’

ESMO open, Apr 1, 2021

C. De Angelis, D. Bruzzese, A. Bernardo, E. Baldini, L. Leo, A. Fabi, T. Gamucci, P. De Placido, ... more C. De Angelis, D. Bruzzese, A. Bernardo, E. Baldini, L. Leo, A. Fabi, T. Gamucci, P. De Placido, F. Poggio, S. Russo, V. Forestieri, R. Lauria, I. De Santo, R. Caputo, D. Cianniello, A. Michelotti, L. Del Mastro, M. De Laurentiis, M. Giuliano, S. De Placido & G. Arpino Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples; Department of Public Health, University of Naples “Federico II”, Naples; Oncologia Medica, Fondazione S. Maugeri IRCCS, Pavia; Department of Oncology, S. Luca Hospital, Lucca; Unit of Oncology, A.O.R.N. dei Colli, Napoli, Naples; Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome; Medical Oncology Unit, ASL Frosinone, Frosinone; UO Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova; Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine; Breast Oncology Department, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Azienda Ospedaliera Universitaria Pisana, Ospedale Santa Chiara, Pisa; University of Genova, Dipartimento di Medicina Interna e Specialità Mediche (DIMI), Genova, Italy

Research paper thumbnail of 212P Real-world progression-free survival 2 with CDK4/6 inhibitors plus endocrine therapy and subsequent line: Results from the multicenter SISTER study

Research paper thumbnail of 236P Trastuzumab deruxtecan in Italian real-world experience: Updated analysis from DE-REAL study

Research paper thumbnail of 224P Clinical features and outcomes in HER2+ mBC patients treated with trastuzumab deruxtecan: A subgroup analysis of the De-REAL study

Research paper thumbnail of 105P CDK4/6 inhibitors in hormone receptor-positive, HER2-negative, locally advanced breast cancer (LABC): Biological and clinical activity, and post-surgical approaches

Research paper thumbnail of 267P AB-ITALY: The impact of drug-drug interaction on abemaciclib treatment in Italian real world experience

Research paper thumbnail of Taxane-based adjuvant therapy for early breast cancer (EBC): A meta-analysis of the predictive effect of ER and HER2 status

Journal of Clinical Oncology, 2010

e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improv... more e11025 Background: Taxane-based adjuvant chemotherapy regimens for EBC yield on average an improvement of disease-free-survival (DFS) and overall survival (OS) as compared to anthracycline-based regimens (De Laurentiis et al., JCO 2008). It has been questioned, however, that this average benefit may results from a markedly improved outcome for some subsets of patients, with others not receiving any advantage. To check this hypothesis, we performed a meta-analysis of the predictive effects both of HER2 and of ER status by pooling subsets data of the available randomized trials (RTs). The efficacy of taxane-based regimens in the subgroup of triple-negative (TN) pts was also evaluated. Methods: We searched the Pubmed database to identify randomized trials that compared taxane-based with non-taxane-based adjuvant chemotherapy regimens for EBC and reported efficacy data according to: HER2 or ER or the combination HER2/ER or the TN status. We also searched the proceedings of major international conferences to i...

Research paper thumbnail of Combined blockade of protein kinase A and bcl-2 by antisense strategy induces apoptosis and inhibits tumor growth and angiogenesis

Clinical cancer research : an official journal of the American Association for Cancer Research, 2001

Protein kinase A type I (PKAI) plays a key role in neoplastic transformation, conveys mitogenic s... more Protein kinase A type I (PKAI) plays a key role in neoplastic transformation, conveys mitogenic signals from different sources, and is overexpressed in the majority of human tumors. Inhibition of PKAI by different tools results in cancer-cell growth inhibition in vitro and in vivo. We and others have recently shown that a novel class of mixed-backbone oligonucleotides targeting the PKAI subunit RIalpha exhibits improved pharmacokinetic properties and antitumor activity accompanied by increased apoptosis in several human cancer types in vitro and in vivo. The role of bcl-2 in the control of apoptosis has been widely documented, and the inhibition of bcl-2 expression and function may have important therapeutic implications. In fact, oligonucleotides antisense bcl-2 have shown antitumor activity in animal models and have successfully completed early clinical trials. Recent studies have demonstrated a direct role of PKA in the regulation of the bcl-2-dependent apoptotic pathway. Therefo...

Research paper thumbnail of Antiangiogenic and antitumor activity of anti-epidermal growth factor receptor C225 monoclonal antibody in combination with vascular endothelial growth factor antisense oligonucleotide in human GEO colon cancer cells

Clinical cancer research : an official journal of the American Association for Cancer Research, 2000

Angiogenesis plays a key role in tumor growth and metastasis. The transforming growth factor alph... more Angiogenesis plays a key role in tumor growth and metastasis. The transforming growth factor alpha (TGF-alpha)-epidermal growth factor receptor (EGFR) autocrine pathway controls in part the production of angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cancer cells. In this study, we have evaluated the antiangiogenic and antitumor activity of monoclonal antibody (MAb) C225, an anti-EGFR chimeric human-mouse MAb, alone and in combination with a human VEGF antisense (AS) 21-mer phosphorothioate oligonucleotide (VEGF-AS) in human GEO colon cancer cells. MAb C225 treatment determined a dose-dependent inhibition of VEGF, bFGF, and TGF-alpha production by GEO cells in vitro. Treatment with VEGF-AS caused a selective inhibition in VEGF expression by GEO cells in vitro. Treatment of immunodeficient mice bearing established, palpable GEO xenografts for 3 weeks with VEGF-AS or with MAb C225 determined a cytostatic reversible inh...

Research paper thumbnail of 8-Chloro-cyclic AMP inhibits autocrine and angiogenic growth factor production in human colorectal and breast cancer

Clinical cancer research : an official journal of the American Association for Cancer Research, 1997

8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protei... more 8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protein kinase A, a signaling protein directly involved in cell proliferation and neoplastic transformation, and that causes growth inhibition in a variety of human cancer cell types. In this report, we have investigated the effects of 8-Cl-cAMP on the expression of several growth factors in human colon (GEO and LS174T) and breast (MDA-MB468) cancer cell lines. 8-Cl-cAMP treatment caused in the three cancer cell lines a significant dose- and time-dependent inhibition in the expression of various endogenous autocrine growth factors, such as transforming growth factor alpha, amphiregulin, and CRIPTO, and of two angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor, at both the mRNA and protein levels. Furthermore, 8-Cl-cAMP treatment markedly inhibited the ability of all three cell lines to invade a basement membrane matrix in a chemoinvasion assay. Fi...