Exploration of targeted anti-tumor therapy最新文献

{"title":"Diagnostic utility of prostate health index density prior to MRI-ultrasound fusion targeted biopsy.","authors":"Benjamin H Press, Soum D Lokeshwar, Lindsey Webb, Ghazal Khajir, Shayan Smani, Olamide Olawoyin, Mursal Gardezi, Syed N Rahman, Michael S Leapman, Preston C Sprenkle","doi":"10.37349/etat.2024.00269","DOIUrl":"10.37349/etat.2024.00269","url":null,"abstract":"<p><strong>Aim: </strong>Prostate biopsy can be prone to complications and thus should be avoided when unnecessary. Although the combination of magnetic resonance imaging (MRI), the prostate health index (PHI), and PHI density (PHID) has been shown to improve detection of clinically significant prostate cancer (csPCa), there is limited information available assessing its clinical utility. We sought to determine whether using PHID could enhance the detection of PCa on MRI ultrasound fusion-targeted biopsy (MRF-TB) compared to other biomarker cutoffs.</p><p><strong>Methods: </strong>Between June 2015 and December 2020, 302 men obtained PHI testing before MRF-TB at a single institution. We used descriptive statistics, multivariable logistic regression, and receiver operating characteristic curves to determine the predictive accuracy of PHID and PHI to detect ≥ Gleason grade group (GGG) 2 PCa and identify cutoff values.</p><p><strong>Results: </strong>Any cancer grade was identified in 75.5% of patients and ≥ GGG2 PCa was identified in 45% of patients. The median PHID was 1.05 [interquartile range (IQR) 0.59-1.64]. A PHID cutoff of 0.91 had a higher discriminatory ability to predict ≥ GGG2 PCa compared to PHI > 27, PHI > 36, and prostate specific-antigen (PSA) density > 0.15 (AUC: 0.707 vs. 0.549 vs. 0.620 vs. 0.601), particularly in men with Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions on MRI (AUC: 0.817 vs. 0.563 vs. 0.621 vs. 0.678). At this cutoff, 35.0% of all the original biopsies could be safely avoided (PHID < 0.91 and no ≥ GGG2 PCa) and csPCa would be missed in 9.67% of patients who would have been biopsied. In patients with PI-RADS 1-2 lesions using a PHID cutoff of 0.91, 56.8% of biopsies could be safely avoided while missing 0 csPCa.</p><p><strong>Conclusions: </strong>These findings suggest that a PHID cutoff of 0.91 improves the selection of patients with elevated prostate-specific antigen who are referred for prostate biopsy, and potentially in patients with PI-RADS 1-2 lesions.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1168-1176"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic and leukemic stem cells homeostasis: the role of bone marrow niche.","authors":"Shaimaa Khattab, Manal El Sorady, Ashraf El-Ghandour, Giuseppe Visani, Pier Paolo Piccaluga","doi":"10.37349/etat.2024.00262","DOIUrl":"10.37349/etat.2024.00262","url":null,"abstract":"<p><p>The bone marrow microenvironment (BMM) has highly specialized anatomical characteristics that provide a sanctuary place for hematopoietic stem cells (HSCs) that allow appropriate proliferation, maintenance, and self-renewal capacity. Several cell types contribute to the constitution and function of the bone marrow niche. Interestingly, uncovering the secrets of BMM and its interaction with HSCs in health paved the road for research aiming at better understanding the concept of leukemic stem cells (LSCs) and their altered niche. In fact, they share many signals that are responsible for interactions between LSCs and the bone marrow niche, due to several biological similarities between LSCs and HSCs. On the other hand, LSCs differ from HSCs in their abnormal activation of important signaling pathways that regulate survival, proliferation, drug resistance, invasion, and spread. Targeting these altered niches can help in better treatment choices for hematological malignancies and bone marrow disorders in general and acute myeloid leukemia (AML) in particular. Moreover, targeting those niches may help in decreasing the emergence of drug resistance and lower the relapse rate. In this article, the authors reviewed the most recent literature on bone marrow niches and their relations with either normal HSCs and AML cells/LSC, by focusing on pathogenetic and therapeutic implications.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1027-1055"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.","authors":"Nithiyanandan Ravi, Parul Gupta, Amanjit Bal, Kuruswamy Thurai Prasad, Mandeep Garg, Rakesh Kapoor, Navneet Singh","doi":"10.37349/etat.2024.00232","DOIUrl":"10.37349/etat.2024.00232","url":null,"abstract":"<p><strong>Aim: </strong>There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses.</p><p><strong>Methods: </strong>Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (<i>n</i> = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); <i>n</i> = 27] and healthy-controls (<i>n</i> = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy.</p><p><strong>Results: </strong>At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days <i>vs.</i> 298 days and median PFS = 97 days <i>vs.</i> 197 days; <i>P</i> = 0.025; hazard ratio (HR) = 2.17].</p><p><strong>Conclusions: </strong>Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"508-521"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing the unmet need in NSCLC progression with advances in second-line therapeutics.","authors":"Kinsley Wang, Alexis Leyba, Robert Hsu","doi":"10.37349/etat.2024.00277","DOIUrl":"https://doi.org/10.37349/etat.2024.00277","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, creating a significant unmet need for effective second-line therapies. This review evaluates current and emerging second-line therapeutic options for advanced or metastatic NSCLC, focusing on their efficacy and potential to improve patient outcomes. Anti-angiogenic drugs like ramucirumab combined with chemotherapy, particularly docetaxel, have shown moderate success. Antibody-drug conjugates (ADCs) targeting specific tumor antigens offer a promising avenue for targeted therapy, while chimeric antigen receptor (CAR)-T cell therapy and T-cell receptor therapy leverage the patient's immune system to combat cancer more effectively. mRNA vaccines, although in early stages, show potential for inducing robust immune responses against cancer-specific antigens. Building on this foundation, recent advancements in molecular testing and the exploration of the tumor microenvironment are opening new therapeutic avenues, further enhancing the potential for personalized second-line treatments in NSCLC. While ADCs and bispecific antibodies are gaining traction, more precise biomarkers are needed to optimize treatment response. Regular monitoring through techniques like liquid biopsies allows real-time tracking of mutations such as EGFR T790M, enabling timely therapeutic adjustments. Additionally, the role of neutrophils and macrophages in the tumor microenvironment is increasingly being recognized as a potential therapeutic avenue, with Smad3 emerging as a key target. Further research into drug sequencing, toxicity management, and biomarker development remains crucial to improving NSCLC treatment outcomes.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1297-1320"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors for Gleason score upgrade from prostate biopsy to radical prostatectomy.","authors":"Shayan Smani, Vinaik Sundaresan, Soum D Lokeshwar, Ankur U Choksi, Jeffrey Carbonella, Joseph Brito, Joseph Renzulli, Preston Sprenkle, Michael S Leapman","doi":"10.37349/etat.2024.00259","DOIUrl":"10.37349/etat.2024.00259","url":null,"abstract":"<p><p>Accurate identification of prostate cancer Gleason grade group remains an important component of the initial management of clinically localized disease. However, Gleason score upgrading (GSU) from biopsy to radical prostatectomy can occur in up to a third of patients treated with surgery. Concern for disease undergrading remains a source of diagnostic uncertainty, contributing to both over-treatment of low-risk disease as well as under-treatment of higher-risk prostate cancer. This review examines the published literature concerning risk factors for GSU from time of biopsy to prostatectomy final pathology. Risk factors identified for Gleason upgrading include patient demographic and clinical factors including age, body mass index, race, prostate volume, and biomarker based assays, including prostate-specific antigen (PSA) density, and testosterone values. In addition, prostate magnetic resonance imaging (MRI) findings have also been associated with GSU. Biopsy-specific characteristics associated with GSU include lower number of biopsy cores and lack of targeted methodology, and possibly increasing percent biopsy core positivity. Recognition of risk factors for disease undergrading may prompt confirmatory testing including repeat sampling or imaging. Continued refinements in imaging guided biopsy techniques may also reduce sampling error contributing to undergrading.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 4","pages":"981-996"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.","authors":"Jingxin Ye, Jianfeng Zhang, Weifeng Ding","doi":"10.37349/etat.2024.00203","DOIUrl":"10.37349/etat.2024.00203","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"34-53"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response.","authors":"Pierluigi De Santis, Martina Perrone, Chiara Guarini, Anna Natalizia Santoro, Carmelo Laface, Daniela Carrozzo, Gaia Rachele Oliva, Palma Fedele","doi":"10.37349/etat.2024.00215","DOIUrl":"10.37349/etat.2024.00215","url":null,"abstract":"<p><p>Triple negative breast cancer (TNBC) represents an aggressive disease associated with a high risk of recurrence after curative treatment and a poor prognosis in the metastatic setting. Chemotherapy was for years the only treatment available in the early and metastatic setting, due to the lack of actionable targets. Clinical practice has changed following the results obtained with the addition of immunotherapy to standard chemotherapy, the development of novel drugs [i.e. antibody-drug conjugates (ADCs)], and the use of targeted treatments for patients carrying germline pathogenic breast cancer susceptibility genes (<i>BRCA</i>) <i>1</i> or <i>BRCA 2</i> variants. The treatment of early-stage disease has had a shift in clinical practice since July 2021, after the Food and Drug Administration (FDA) approval of pembrolizumab in association with chemotherapy as neoadjuvant treatment for TNBC and as a single agent in the subsequent adjuvant setting. This intensive treatment based on the combination of a poly-chemotherapy and an immune checkpoint inhibitor (ICI) led to the improvement of short- and long-term outcomes, but it has highlighted some new unmet clinical needs in the treatment of early-stage TNBC: the selection of the most effective adjuvant therapy and the integration of pembrolizumab with other therapeutic strategies [capecitabine, poly(ADP-ribose) polymerase (PARP) inhibitors] based on the achievement of pathologic complete response (pCR); the identification of predictive biomarkers to select patients who could most benefit from the addition of ICI, to minimize toxicities and to maximize outcomes; the possibility of de-escalating chemotherapy in favor of immune-combo or novel agents, such as ADCs; the role of immunotherapy in estrogen receptor (ER)-low patients. The advent of immunotherapy not only addresses current challenges in TNBC treatment but also holds the promise of a radical transformation in its therapeutic paradigm, enhancing significantly clinical outcomes and offering new perspectives for patients grappling with this aggressive form of breast cancer.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"232-250"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of stage III non-small-cell lung cancer: rays of hope.","authors":"Floryane Kim, Maxime Borgeaud, Alfredo Addeo, Alex Friedlaender","doi":"10.37349/etat.2024.00206","DOIUrl":"10.37349/etat.2024.00206","url":null,"abstract":"<p><p>Lung cancer remains the most common cause of cancer death across the world. Non-small-cell lung cancer (NSCLC) represents the most frequent type of lung cancer and is frequently diagnosed at an advanced stage. Stage III NSCLC, which encompasses 30% of cases, refers to a state between localized and metastatic disease, and is associated with poor prognosis. As highlighted in this review, stage III represents a heterogenous group, whose complex management includes multimodal treatment, discussed below, and requires discussion in multidisciplinary teams. The goal of this approach is a maximalist attitude in these patients with locally advanced and non-metastatic disease. However, many issues remain under debate including the optimal sequences of treatment between different treatment modalities, patient selection particularly for surgery, the duration of perioperative treatments and the identification of biomarkers to determine which patients might benefit of specific treatment like immunotherapy and targeted therapies. This review describes the current landscape of management of stage III NSCLC, discussing the critical issue of resectability, and highlighting the recent advancements in the field, particularly the incorporation of immune-checkpoint inhibitors (ICIs) and targeted therapies in this setting.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 1","pages":"85-95"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status of molecular diagnostics for lung cancer.","authors":"Evgeny N Imyanitov, Elena V Preobrazhenskaya, Sergey V Orlov","doi":"10.37349/etat.2024.00244","DOIUrl":"10.37349/etat.2024.00244","url":null,"abstract":"<p><p>The management of lung cancer (LC) requires the analysis of a diverse spectrum of molecular targets, including kinase activating mutations in <i>EGFR</i>, <i>ERBB2</i> (<i>HER2</i>), <i>BRAF</i> and <i>MET</i> oncogenes, <i>KRAS</i> G12C substitutions, and <i>ALK</i>, <i>ROS1</i>, <i>RET</i> and <i>NTRK1-3</i> gene fusions. Administration of immune checkpoint inhibitors (ICIs) is based on the immunohistochemical (IHC) analysis of PD-L1 expression and determination of tumor mutation burden (TMB). Clinical characteristics of the patients, particularly age, gender and smoking history, significantly influence the probability of finding the above targets: for example, LC in young patients is characterized by high frequency of kinase gene rearrangements, while heavy smokers often have <i>KRAS</i> G12C mutations and/or high TMB. Proper selection of first-line therapy influences overall treatment outcomes, therefore, the majority of these tests need to be completed within no more than 10 working days. Activating events in MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option for some laboratories. RNA next-generation sequencing (NGS) is capable of detecting the entire repertoire of druggable gene alterations, therefore it is gradually becoming a dominating technology in LC molecular diagnosis.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 3","pages":"742-765"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of the PARPi and ARSi in advanced castration resistant prostate cancer: a review of the recent phase III trials.","authors":"Martina Panebianco, Vittore Cereda, Mario Rosario D'Andrea","doi":"10.37349/etat.2024.00260","DOIUrl":"10.37349/etat.2024.00260","url":null,"abstract":"<p><p>Tumors with an impaired ability to repair DNA double-strand breaks by homologous recombination, including those with alterations in breast cancer 1 and 2 (<i>BRCA1</i> and <i>BRCA2</i>) genes, are very sensitive to blocking DNA single-strand repair by inhibition of the poly (ADP-ribose) polymerase (PARP) enzyme. This provides the basis for a synthetic deadly strategy in the treatment of different types of cancer, such as prostate cancer (PCa). The phase 3 PROfound study was the first to lead to olaparib approval in patients with metastatic castration resistant PCa (mCRPC) and <i>BRCA</i> genes mutations. In recent years, the benefit of combination therapy consisted of a PARP inhibitor (PARPi) plus an androgen receptor signalling inhibitor (ARSi), was evaluated as first-line treatment of mCRPC, regardless of the mutational state of genes, participating in the homologous recombination repair (HRR). This review explores the role of PARPi in PCa and analyses the data of latest clinical trials exploring the PARPi-ARSi combinations, and how these results could change our clinical practice.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"997-1010"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}