Vincenza Conteduca

Università degli studi di Foggia | UNIFG · Department of Medical and Surgical Sciences

Aberrations in the homologous recombination repair (HRR) pathway in prostate cancer (PCa) provide a unique opportunity to develop therapeutic strategies that take advantage of the reduced tumor ability to repair DNA damage. Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have been shown to prolong the survival of PCa patients with HRR defects,...

10543 Background: Homologous recombination repair (HRR) defects are driver mutational imprints and actionable biomarkers in prostate cancer (PrC) patients. However, recent research provides evidence of PrC onset also in the context of mismatch repair deficiency (MMRd). In the current report, we investigated whether the position of pathogenic varian...

5068 Background: Liquid biopsies enable non-invasive detection of circulating biomarkers for disease monitoring and treatment resistance interrogation. We aimed to study circulating tumour DNA (ctDNA) and its early changes during treatment to identify biomarkers of resistance to cabazitaxel in mCRPC patients (pts). We also designed and validated a...

Background The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging. Objectives The primary objective was to assess the effectiveness of the lenvatinib plus everolimus combination and the secondary objective was the toxicity profile of this combination. Desi...

Background Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signa...

Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to th...

158 Background: ECHOS trial is a large real-world study, which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, > 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed...

Background: PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE),...

PARP inhibitors (PARPis) are effective treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) as single agents or in combination with androgen receptor-targeted agents (ARTA). However, a clinically relevant adverse effect of these agents is hematological toxicity, a typical class adverse event (AE), which can le...

Background Baseline plasma androgen-receptor copy number (AR-CN) is a promising biomarker for metastatic castration-resistant prostate cancer (mCRPC) outcome and treatment response; however, the role of its longitudinal testing is unproven. We aimed to evaluate the prognostic role of AR-CN assessed before subsequent treatment lines in mCRPC patient...

The main guidelines and recommendations for the implementation of the BRCA1/2 somatic test do not focus on the clinical application of predictive testing on bone metastases, a frequent condition in metastatic prostate cancer, by analyzing the critical issues encountered by laboratory practice. Our goal is to produce a document (protocol) deriving f...

Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of prostate cancer intracranial metastases would improve our understanding of their pathogenesis and the search for new treatment strategies. We evaluated the clinical and molecular characteristics of 36 patients with metastatic...

Up to 80% of castration-resistant prostate cancer (CRPC) patients develop bone metastases during the natural history of disease and about 25% harbor mutations in DNA damage repair (DDR) genes. This retrospective observational study evaluated the prevalence of DDR alterations in CRPC patients and their effect on the clinical outcomes associated with...

Prostate cancer is the most commonly diagnosed cancer but the management of advanced prostate cancer remains a therapeutic challenge, despite the survival benefits imparted by several therapeutic discoveries targeting different molecular pathways. The mechanisms of resistance to androgen deprivation and tumour progression to lethal metastatic varia...

e16539 Background: Cabozantinib is approved as first-line therapy for patients with intermediate-poor risk metastatic renal cell carcinoma (mRCC); however translating results from pivotal trials to an unselected real-world population remains a concern. Methods: CabFRONT is a retrospective observational multicentre Italian Network for Research in Ur...

Purpose: Patients with neuroendocrine prostate cancer (NEPC) are often managed with immunotherapy regimens extrapolated from small cell lung cancer (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared to other prostate cancer types and SCLC. Experimental design: In this retrospective study, a cohort of 170 patients with 230...

Background: At diagnosis, more than 80% of patients with pancreatic cancer (PC) suffer from significant weight loss due to malnutrition which is a major concern for patient management, and this may negatively impact treatment outcomes and patient prognosis. Patients and methods: We performed an observational, retrospective study on patients with...

214 Background: Up to 80% of mCRPC have bone metastases and about 25% of metastatic prostate cancer harbor mutations in DNA damage repair defects (DDR). DDR gene mutations are a negative prognostic factor, being associated with short metastasis-free survival and cancer-specific survival. We analyzed the impact of somatic mutations in DDR genes on b...

223 Background: The need for genetic prognostic and predictive markers is urgent in order to identify potential target therapies or personalized therapeutic sequences for men with metastatic prostate cancer (mPC). The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) such as germline mutations in BRCA2 (gBRCA) is well establis...

Simple Summary A mass spectrometry (MS) proteomics and molecular pathway study was applied to serum samples of patients with ovarian serous carcinoma administered the FOLFOX-4 drug combination protocol, before the second cycle of therapy. This exploratory study aimed at identifying a protein panel that could be significantly modulated during two di...

Background: There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). Methods: We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG...

Background: Immunotherapy has not achieved improvement of survival in prostate cancer patients. Myeloid-derived suppressor cells (MDSCs) in tumor microenvironment can hamper its efficacy. Some preclinical studies explored the role of MDSCs in prostate cancer development. We aimed to verify the availability of studies exploring the prognostic effec...

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating...

Simple summary Low-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade s...

Background Novel androgen receptor signaling inhibitors for prostate cancer (PC) impose the burden of self-administration on older patients overwhelmed by the requirement of many other concomitant medications. Patients and Methods This study evaluated the proportion of non-adherence in a 12-month follow-up period and the first 3 months to abirater...

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a "consensus" classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order t...

Lichenoid reactions are one of the most frequently observed toxicities with anticancer agents and, recently, a rapid emergence of immunotherapies in oncology has hastened the need to better characterize their unique toxicity profiles, particularly for less common skin toxicities, including anogenital lichen sclerosus et atrophicus (LSA). This case...

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitution...

e17038 Background: Programmed death-ligand 1 (PD-L1) has been recently found in tumor-derived exosomes and associated with progressive disease (PD) ( Poggio, Cell 2019). In localized prostate cancer, PD-L1 tumor expression has been shown to be a biomarker for node-positive patients (pts) ( Petitprez, Eur Urol Focus 2019) but its role in mCRPC is la...

In localized prostate cancer (PCa), Grade Group (GG) and Gleason Score (GS) have a well-established prognostic role. In metastatic castration resistant prostate cancer (mCRPC), the prognostic role of GS and GG is less defined. In first-line treatment of mCRPC, androgen receptor (AR)-directed drugs (abiraterone acetate, enzalutamide) and docetaxel r...

Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples. We divid...

152 Background: Accurate monitoring response of bone mets to treatment is an active need for mCRPC patients (pts). Recently, ctDNA has been showed as an early biomarker efficacy of androgen receptor signaling inhibitor (ARSI) therapy for mCRPC ( Conteduca, Br J Cancer 2020). In this study, we aimed to reveal if ctDNA analysis can permit more reliab...

Abstract Background Cabazitaxel improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel. In this prospective study, we evaluated the prognostic role of CTC gene expression on cabazitaxel-treated patients and its association with plasma androgen receptor (AR) copy number (CN). Me...

Purpose: Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has important clinical implications, but is challenging to detect in practice. Herein, we report a novel tissue-informed epigenetic approach to non-invasively detect NEPC. Experime...

Plasma tumour DNA (ptDNA) is a potential early non‐invasive biomarker of treatment outcome in metastatic castration‐resistant prostate cancer (mCRPC). Herein, we investigated whether pre‐treatment ptDNA levels reflect metabolic tumour burden in mCRPC and better predict treatment outcome in combination with functional imaging. Targeted next‐generati...

Cancer is a risk factor for venous thromboembolism (VTE). Plasma tumor DNA (ptDNA) is an independent predictor of outcome in metastatic castration‐resistant prostate cancer (mCRPC). We aimed to investigate the association between ptDNA and VTE in mCRPC. This prospective biomarker study included 180 mCRPC patients treated with abiraterone and enzalu...

Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and pre...

Introduction Melphalan, as a bifunctional alkylating agent has been shown to be selectively efficient in BRCA-deficient case reports of epithelial ovarian cancer (EOC). The clinical benefit of melphalan on unselected platinum-resistant EOC population and stratified by BRCA status has not been clearly elucidated. We aimed to determine the response t...

Background Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown. Patients and methods Th...

Epigenetic alterations, including changes in DNA methylation, histone modifications and nucleosome remodeling, result in abnormal gene expression patterns that contribute to prostate tumor initiation and continue to evolve during the course of disease progression. Epigenetic modifications are responsible for silencing tumor-suppressor genes, activa...

In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [¹⁷⁷Lu]-PSMA-617 activity and the clinical utility of levels of plasma androgen receptor (AR) gene in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). We determined AR copy number in pretreatment plasma samples. We used logistic regression t...

Despite advances in the development of highly effective androgen receptor (AR)-directed therapies for the treatment of men with advanced prostate cancer, acquired resistance to such therapies frequently ensues. A significant subset of patients with resistant disease develop AR-negative tumors that lose their luminal identity and display neuroendocr...

Background: Circulating Tumor Cells (CTCs) correlate with adverse prognosis in breast, colorectal, lung and prostate cancer patients. Little data is available for Renal Cell Carcinoma (RCC). Materials and methods: We designed a multicenter prospective observational study to assess the correlation between CTC counts and Progression Free Survival...

Background Androgen receptor (AR) signaling inhibitors represent the standard treatment in metastatic castration resistance prostate cancer (mCRPC) patients. However, some patients display a primary resistance, and several studies investigated the role of the AR as a predictive biomarker of response to treatment. This study is aimed to evaluate the...

Introduction: Prostate cancer is one of the most frequent tumors worldwide. Due to the lack of reliable markers, patients are usually diagnosed at a late stage when it becomes castration-resistant prostate cancer (CRPC) with a worse outcome. Thus, it is essential to ameliorate the clinical management of these patients. Nowadays, the use of liquid b...

5048 Background: Cancer is a risk factor for VTE. In mCRPC, ptDNA is an independent predictor of outcome ( Romanel, Sci Transl Med 2015; Conteduca, Br J Cancer 2020). We firstly aimed to investigate the association between ptDNA and VTE in mCRPC men treated with androgen receptor signaling inhibitors (ARSI) Methods: This prospective biomarker study...

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Inde...

Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological me...

141 Background: Recently, plasma tumour DNA (ptDNA) has been identified as a potential early noninvasive biomarker of treatment response in mCRPC patients ( Conteduca, Br J Cancer 2020). In this study, we sought to determine whether pre-treatment ptDNA could accurately reflect metabolic tumor burden in mCRPC and if it could be in combination with f...

Simple Summary Gynecological cancers represent a group of malignancies with high incidence and mortality, despite their relative sensitivity to platinum-based chemotherapy. This review aims to illustrate the state of research in the field of immunotherapy, and in particular, deals with the development of CAR-T cell therapy, which represents a very...

Prostate cancer is one of the most frequent cancers in men and is a common cause of cancer-related death. Despite significant progress in the diagnosis and treatment of this tumor, patients who relapse after radical treatments inevitably develop metastatic disease. Patient stratification is therefore key in this type of cancer, and there is an urge...

Analysis of androgen receptor (AR) status, particularly AR copy number, in plasma DNA is a minimally invasive method with the potential to identify treatment resistance in patients with castration-resistant prostate cancer (CRPC) starting enzalutamide or abiraterone. Patients with elevated plasma AR do not have worse outcomes than patients with nor...

The rapidly expanding scenario of treatment options for patients affected by prostate cancer (PC) is leading to improved outcomes; however, PC still represents one of the most frequent causes of male mortality. Thus, while translational research is trying to unravel the molecular landscape underlying carcinogenesis, disease progression and treatmen...

Background Taxanes are the most active chemotherapy agents in metastatic castration-resistant prostate cancer (mCRPC) patients; yet, resistance occurs almost invariably, representing an important clinical challenge. Taxane-platinum combinations have shown clinical benefit in a subset of patients, but the mechanistic basis and biomarkers remain elus...

Introduction: Plasma androgen receptor (AR) copy number (CN) status identifies castration-resistant prostate cancer (CRPC) patients with worse outcome on abiraterone/enzalutamide. However, the impact of AR CN changes on clinical outcome in CRPC is unknown. Materials and Methods: Plasma samples from 73 patients treated with abiraterone or enzalutami...

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in...

Introduction Enzalutamide is the first characterized second-generation nonsteroidal androgen receptor inhibitor (ARi). Its efficacy has been established in several clinical trials evaluating its role in different settings of prostate cancer. Recently, enzalutamide has been approved for the treatment of nonmetastatic castration-resistant prostate ca...

Plasma tumour DNA (ptDNA) levels on treatment are associated with response in a variety of cancers. However, the role of ptDNA in prostate cancer monitoring remains largely unexplored. Here we characterised on-treatment ptDNA dynamics and evaluated its potential for early assessment of therapy efficacy for metastatic castration-resistant prostate c...

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disord...

Background Immune checkpoint inhibitors (ICIs) have been revolutionizing the treatment landscape of metastatic renal cell carcinoma (mRCC). The use of ICIs in elderly RCC patients has become a daily practice, although their real impact in elderly patients is nowadays not completely clarified. It has been hypothesized that ICIs might not perform as...

5546 Background: Plasma AR status has been identified as a potential biomarker of response in CRPC patients receiving docetaxel or the AR-targeted therapies abiraterone or enzalutamide. However, the relevance of plasma AR in the overall management of CRPC patients (pts) receiving docetaxel at different dose due to the toxicity profiles and physicia...

Tumor DNA circulates in the plasma of cancer patients admixed with DNA from noncancerous cells. The genomic landscape of plasma DNA has been characterized in metastatic castration-resistant prostate cancer (mCRPC) but the plasma methylome has not been extensively explored. Here, we performed next-generation sequencing (NGS) on plasma DNA with and w...

Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer of tumor cells to DNA damaging agents including platinum chemotherapy. We assessed the impact of SLFN11 expression on response to platinum chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor...

Loss of androgen receptor (AR) signaling dependence occurs in approximately 15%-20% of advanced treatment-resistant prostate cancers, and this may manifest clinically as transformation from a prostate adenocarcinoma histology to a castration-resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE currently relies on a metastati...

154 Background: Cabazitaxel demonstrated overall survival (OS) benefit for the treatment of CRPC progressing after docetaxel. CTC profiling could help to establish novel predictive biomarkers. In this prospective study (NCT03381326), we evaluated the prognostic role of CTC biomarkers expression and the association with plasma AR CN in pts treated w...

8 Background: Loss of androgen receptor signaling dependence occurs in approximately 20% of treatment resistant prostate cancers, and this may manifest as transformation to castration resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE relies on a metastatic tumor biopsy, which is invasive for patients. Here we study ctDNA...

Treatment options for metastatic renal cell carcinoma (RCC) have been expanding in the last years, from the consolidation of several anti-angiogenic agents to the approval of immune checkpoint inhibitors (ICIs). The rationale for the use of immunomodulating agents derived from the observation that RCC usually shows a diffuse immune-cell infiltrate....

Loss of androgen receptor (AR) signaling dependence occurs in approximately 15-20% of treatment resistant prostate cancers, and this may manifest clinically as transformation from a prostate adenocarcinoma histology to a castration resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE currently relies on a metastatic tumor bi...

The therapeutic landscape of prostate cancer has expanded rapidly over the past 10 years, and there is now an even greater need to understand the biological mechanisms of resistance and to develop noninvasive biomarkers to guide treatment. The androgen receptor (AR) is known to be involved in the pathogenesis and progression of prostate cancer. Rec...

Background Tumour DNA circulates in the plasma of cancer patients admixed with DNA from non-cancerous cells. The genomic landscape of plasma tumour DNA has been characterised in metastatic castration-resistant prostate cancer (mCRPC) but the plasma methylome in mCRPC has not been extensively explored. Methods mCRPC plasma samples collected from th...

Background Ra223 is a bone-seeking a-emitter targeted therapy that induces double-strand DNA breaks (DSBs). The HR pathway is used to accurately repair DSBs and a significant proportion of mCRPC patients harbor pathogenic germline HR mutations (gHR+). We hypothesize that gHR+ patients, with an impaired ability to repair DSBs, are more likely to res...

Background Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and drug resistance. NEPC is an aggressive variant of prostate cancer that may develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. Loss of tumour suppressors RB1, TP53, PTEN are frequent in NEPC but also present in a subse...

Background Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer, but limited studies have been performed to investigate the association between ADT and immune alterations, such as autoimmune diseases and risk of second tumours, considering that androgens may also play a role in the immune modulation. Methods We retr...

Background Abiraterone and enzalutamide represent the standard treatment in castration resistance prostate cancer (CRPC) patients, however, some patient displays primary resistance, and several studies investigated the role of the androgen receptor (AR) as a predictive biomarker of response to treatment (Conteduca, et al. Ann Oncol. 2017;28(7):1508...

PURPOSE Increases in androgen receptor ( AR) copy number (CN) can be detected in plasma DNA when patients develop metastatic castration-resistant prostate cancer. We aim to evaluate the association between AR CN as a continuous variable and clinical outcome. PATIENTS AND METHODS PCR2023 was an international, multi-institution, open-label, phase II...

Background: This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. Methods: 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favora...