Review
Oncology
Mathieu Roumiguie, Xavier Paoletti, Yann Neuzillet, Romain Mathieu, Sebastien Vincendeau, Francois Kleinclauss, Arnaud Mejean, Laurent Guy, Marc Olivier Timsit, Thierry Lebret
Summary: The study compared the efficacy, safety, and health-related quality of life of apalutamide, enzalutamide, and darolutamide in patients with nonmetastatic castration-resistant prostate cancer. Results showed that all three drugs significantly prolonged survival compared to placebo and were generally well tolerated. Therefore, drug selection in clinical practice should be based on individual patient factors such as tolerability, drug interactions, and comorbidities.
Review
Oncology
Carlo Cattrini, Orazio Caffo, Ugo De Giorgi, Alessia Mennitto, Alessandra Gennari, David Olmos, Elena Castro
Summary: This review discusses the use of apalutamide, darolutamide, and enzalutamide in patients with nmCRPC and the clinical implications of novel imaging techniques for treatment selection.
Article
Oncology
Ke Gao, Xiaoshun Li, Jianxin Ni, Bin Wu, Jiaheng Guo, Rui Zhang, Guojun Wu
Summary: This article introduces the roles of dysregulation of different subclasses of non-coding RNAs (ncRNAs) in the development of castration-resistant prostate cancer (CRPC) progression and Enzalutamide (Enz) resistance. The mechanisms of Enz resistance, including AR-splice variant-7 (AR-V7), mutations, circRNAs, and lncRNAs that act as miRNA sponges, are discussed. The contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are also highlighted. The article summarizes the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and discusses future therapeutic strategies against Enz resistance.
Article
Oncology
Jing Wei, Lijuan Yin, Jingjing Li, Jing Wang, Tianjie Pu, Peng Duan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: The study reveals a reciprocal regulatory circuit between MAOA and AR in prostate cancer, with implications for cancer development and growth, particularly CRPC. Targeting MAOA may enhance the efficacy of AR-targeted therapies.
Article
Oncology
Petra Deegen, Oliver Thomas, Olivier Nolan-Stevaux, Shyun Li, Joachim Wahl, Pamela Bogner, Famke Aeffner, Matthias Friedrich, Michael Z. Liao, Katja Matthes, Doris Rau, Benno Rattel, Tobias Raum, Peter Kufer, Angela Coxon, Julie M. Bailis
Summary: AMG 160, a bispecific T-cell engager immuno-oncology therapy targeting PSMA in mCRPC, demonstrates potent antitumor activity in vitro and in vivo. It shows enhanced cytotoxic activity when combined with diagnostic or therapeutic agents such as the PSMA-imaging agent, novel hormonal therapy, and immune checkpoint blockade. Preclinical data supports ongoing clinical evaluation in patients with mCRPC.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Felix Y. Feng, Shibu Thomas, Fred Saad, Michael Gormley, Margaret K. Yu, Deborah S. Ricci, Brendan Rooney, Sabine Brookman-May, Sharon McCarthy, David Olmos, Simon Chowdhury, Boris Hadaschik, Yang Liu, Elai Davicioni, Matthew R. Smith, Eric J. Small
Summary: The GC score and basal-luminal subtype derived from archived tumor specimens could be potential biomarkers for predicting response to apalutamide+ADT in nmCRPC patients. Although the addition of apalutamide to ADT was beneficial overall, higher-risk and luminal subtypes appeared to benefit most.
Article
Urology & Nephrology
Susan Halabi, Shan Jiang, Emi Terasawa, Viviana Garcia-Horton, Rajeev Ayyagari, A. Reginald Waldeck, Neal Shore
Summary: This study compared the safety and efficacy of darolutamide vs apalutamide, and darolutamide vs enzalutamide in nonmetastatic castration-resistant prostate cancer through matching-adjusted indirect comparisons. While there were no differences in metastasis-free survival, darolutamide showed lower rates of certain adverse events compared to apalutamide and enzalutamide, suggesting a more favorable safety and tolerability profile.
JOURNAL OF UROLOGY
(2021)
Article
Endocrinology & Metabolism
Yifan Zhang, Yuanpeng Liao, Mayao Luo, Yuedian Ye, Zhuofan Xu, Wenli Hou, Ruiyu Liu, Qiliang Zhai, Shidong Lv, Qiang Wei
Summary: The combination of AR degrader IU1 and AR antagonist enzalutamide synergistically promotes AR degradation and inhibits proliferation, induces apoptosis, and blocks the cell cycle in prostate cancer cells. Mechanistically, the combination treatment increases AR ubiquitination levels, resulting in the inhibitory effect on prostate cancer cells.
Article
Oncology
Anthony Serritella, Daniel Shevrin, Elisabeth Heath, James L. Wade, Elia Martinez, Amanda Anderson, Joseph Schonhoft, Yen-Lin Chu, Theodore Karrison, Walter M. Stadler, Russell Z. Szmulewitz
Summary: This study evaluated the effectiveness of dual androgen receptor (AR) and glucocorticoid receptor (GR) antagonism in castration-resistant prostate cancer (CRPC). The combination of enzalutamide and mifepristone was found to be safe and well-tolerated, but did not meet the primary endpoint. Further research should explore the use of more specific GR antagonists combined with AR antagonists in earlier disease stages.
CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Doo Yong Chung, Jee Soo Ha, Kang Su Cho
Summary: The treatment goals for patients with non-metastatic castration-resistant prostate cancer are to delay metastasis, preserve quality of life, and increase overall survival. Second-generation androgen receptor inhibitors have shown substantial improvements in clinical trials, with high safety profile and ability to delay disease progression.
Article
Medicine, General & Internal
Kelli M. Rasmussen, Vikas Patil, Chunyang Li, Christina Yong, Sreevalsa Appukkutan, Jamie Partridge Grossman, Jay Jhaveri, Ahmad S. Halwani
Summary: This study examines clinical outcomes by race and ethnicity in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) within the US Veterans Health Administration. The results suggest that there are differences in outcomes by race and ethnicity, and Black and Hispanic men may have considerably improved outcomes when treated in an equal-access setting.
Article
Oncology
Sarah E. Kohrt, Wisam N. Awadallah, Robert A. Phillips, Thomas C. Case, Renjie Jin, Jagpreet S. Nanda, Xiuping Yu, Peter E. Clark, Yajun Yi, Robert J. Matusik, Philip D. Anderson, Magdalena M. Grabowska
Summary: A short hairpin RNA screen identified 11 genes supporting enzalutamide resistance, with validation experiments confirming the roles of ACAT1, MAP3K11, and PSMD12 in vitro. Inhibition of MAP3K11 in combination with enzalutamide led to increased cell death, suggesting potential therapeutic strategies for castration-resistant prostate cancer.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Medicine, Research & Experimental
Sue Jin Moon, Byong Chang Jeong, Hwa Jin Kim, Joung Eun Lim, Hye-Jeong Kim, Ghee Young Kwon, Joshua A. Jackman, Jeong Hoon Kim
Summary: The study identified BCT as a potent inhibitor targeting both AR-FL and AR-V7 activities in CRPC, effectively suppressing tumor growth and metastasis. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7, leading to their degradation and showing promising therapeutic potential against CRPC.
Article
Oncology
Neeraj Agarwal, Arun Azad, Neal D. Shore, Joan Carles, Andre P. Fay, Curtis Dunshee, Lawrence Ivan Karsh, Maria Luisa Paccagnella, Nicola Di Santo, Mohamed Elmeliegy, Xun Lin, Akos Czibere, Karim Fizazi
Summary: The TALAPRO-2 study is designed to compare the efficacy of talazoparib plus enzalutamide versus placebo plus enzalutamide as first-line treatment for mCRPC patients, with a focus on radiographic progression-free survival.
Article
Oncology
Tie Zhou, Shengfei Qin, Weidong Xu, Shouyan Tang, Guanghua Chen, Song Li, Jianguo Hou, Xu Gao, Guowei Shi, Zhongquan Sun, Jie Jin, Lijun Chen, Weibing Sun, Ben Liu, Jingen Wang, Qinggui Meng, Dongwen Wang, Zhiquan Hu, Dalin He, Yong Yang, Xishuang Song, Cheng Fu, Yinhuai Wang, Dingwei Ye, Wei Zhang
Summary: This study assessed the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, in men with metastatic castration-resistant prostate cancer (mCRPC). By evaluating various endpoints, it was found that the 200 mg dose group showed the best antitumor activity with manageable safety. Therefore, a daily dose of 200 mg proxalutamide is recommended for future phase 3 trials.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Giorgia Gurioli, Vincenza Conteduca, Nicole Brighi, Emanuela Scarpi, Umberto Basso, Giuseppe Fornarini, Alessandra Mosca, Maurizio Nicodemo, Giuseppe Luigi Banna, Cristian Lolli, Giuseppe Schepisi, Giorgia Ravaglia, Isabella Bondi, Paola Ulivi, Ugo De Giorgi
Summary: This study evaluated the prognostic role of CTC gene expression in cabazitaxel-treated mCRPC patients and its association with plasma AR copy number. The results showed that CTC gene expression was significantly associated with overall survival and disease progression. AR-V7 was identified as an important prognostic biomarker, and patients with AR-V7 positivity had poorer outcomes with lower dose cabazitaxel treatment.
Review
Oncology
Giuseppe Bronte, Vincenza Conteduca, Matteo Landriscina, Antonio Domenico Procopio
Summary: This meta-analysis demonstrates that high levels of circulating MDSCs are associated with worse overall survival in prostate cancer patients, supporting the importance of MDSC detection and targeting in this population.
PROSTATE CANCER AND PROSTATIC DISEASES
(2023)
Article
Oncology
Domenico D'Arca, Leda Severi, Stefania Ferrari, Luca Dozza, Gaetano Marverti, Fulvio Magni, Clizia Chinello, Lisa Pagani, Lorenzo Tagliazucchi, Marco Villani, Gianluca d'Addese, Isabella Piga, Vincenza Conteduca, Lorena Rossi, Giorgia Gurioli, Ugo De Giorgi, Lorena Losi, Maria Paola Costi
Summary: In this study, mass spectrometry and molecular pathway analysis were used to analyze serum samples from patients with ovarian serous carcinoma before the second cycle of FOLFOX-4 therapy. A total of 291 shared expressed proteins were identified, and 12 proteins were found to be significantly associated with treatment response and sample collection time. Network enrichment analysis revealed that these proteins were related to drug-resistant ovarian cancer at the molecular level. This study suggests a new direction for the discovery of protein biomarkers for predicting treatment response.
Article
Oncology
Bhavneet Bhinder, Alison Ferguson, Michael Sigouros, Manik Uppal, Ahmed G. Elsaeed, Rohan Bareja, Hussein Alnajar, Kenneth Wha Eng, Vincenza Conteduca, Andrea Sboner, Juan Miguel Mosquera, Olivier Elemento, Himisha Beltran
Summary: This study analyzed the RNA-sequencing and whole-exome sequencing data of 170 patients with neuroendocrine prostate cancer (NEPC). It found that NEPC has a unique tumor immune landscape compared to other prostate cancer types and small-cell lung cancer (SCLC). NEPC is characterized by a relatively immune-depleted tumor immune microenvironment and less mutations, but has comparable expression of checkpoint genes PD-L1 and CTLA-4 with SCLC. These findings can inform the development of immunotherapy strategies for NEPC.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Guido Giordano, Raffaele Ivan Cincione, Francesca Losavio, Tiziano Senia, Arianna Aquilini Mummolo, Mario Pacilli, Vincenzo Lizzi, Giuseppina Bruno, Annamaria Piscazzi, Vincenza Conteduca, Matteo Landriscina
Summary: Patients with pancreatic cancer often suffer from malnutrition and significant weight loss, which negatively affect treatment outcomes. This study found that nutritional support and pancreatic enzyme replacement therapy can improve overall survival and nutritional parameters in patients with metastatic pancreatic cancer. Early and well-conducted nutritional support can positively impact survival and quality of life.
Review
Immunology
Giuseppe Schepisi, Caterina Gianni, Maria Concetta Cursano, Valentina Galla, Cecilia Menna, Chiara Casadei, Sara Bleve, Cristian Lolli, Giovanni Martinelli, Giovanni Rosti, Ugo De Giorgi
Summary: Germ cell tumors (GCTs) are a heterogeneous neoplasm family that primarily affects the gonads and rarely occurs in extragonadal areas. Although most patients have a good prognosis, about 15% of cases experience tumor relapse and platinum resistance. Therefore, there is a need for novel treatment strategies with improved antineoplastic activity and fewer treatment-related adverse events. This article discusses the immune mechanisms underlying GCT development and reviews studies on new immunotherapeutic approaches in these tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Giuseppe Schepisi, Caterina Gianni, Michela Palleschi, Sara Bleve, Chiara Casadei, Cristian Lolli, Laura Ridolfi, Giovanni Martinelli, Ugo De Giorgi
Summary: To date, various therapeutic strategies, including immunotherapies, have been successful in prolonging the survival of breast cancer patients. Our article focuses on the application of chimeric antigen receptor-based immunotherapy in breast cancer.
Review
Oncology
Vincenza Conteduca, Nicole Brighi, Giuseppe Schepisi, Ugo De Giorgi
Summary: Prostate cancer is a common cancer, but the management of advanced prostate cancer is still challenging despite therapeutic discoveries. Resistance to androgen deprivation and the progression of tumors are often regulated by androgen receptor bypass mechanisms and neuroendocrine differentiation. Recent data suggests the involvement of immune cells in prostate tumor progression. Improved cancer genome analyses contribute to a better understanding of antitumor immunity and provide solutions for targeting cancer-specific neoantigens.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Maria Concetta Cursano, Emilio Francesco Giunta, Emanuela Scarpi, Chiara Casadei, Alessandra Virga, Paola Ulivi, Sara Bleve, Nicole Brighi, Giorgia Ravaglia, Francesco Pantano, Vincenza Conteduca, Daniele Santini, Ugo De Giorgi
Summary: This study evaluated the prevalence of DNA damage repair (DDR) gene mutations in castration-resistant prostate cancer (CRPC) patients and their impact on clinical outcomes related to bone metastases. The results showed that DDR mutations were associated with larger bone metastases volume, but did not affect skeletal-related events incidence and time to onset.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Nicole Brighi, Giuseppe Lamberti, Elisa Andrini, Cristina Mosconi, Lisa Manuzzi, Giada Donati, Andrea Lisotti, Davide Campana
Summary: In this prospective study, the predictive role of MGMT-promoter methylation in TEM-based chemotherapy for NET patients was investigated. The results showed that MGMT-promoter methylation predicted the treatment response to TEM chemotherapy, and was associated with longer progression-free survival and overall survival.
Review
Biochemistry & Molecular Biology
Milena Urbini, Sara Bleve, Giuseppe Schepisi, Cecilia Menna, Giorgia Gurioli, Caterina Gianni, Ugo De Giorgi
Summary: Cisplatin-based chemotherapy combinations have greatly improved the outcome of metastatic testicular germ cell tumor patients. However, predicting the prognosis of patients who relapse after first-line therapy remains complex. Molecular selection of patients and validated biomarkers are needed to improve risk stratification and identify novel therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Giuseppe Luigi Banna, Umberto Basso, Emilio Francesco Giunta, Lucia Fratino, Sara Elena Rebuzzi, Sebastiano Buti, Marco Maruzzo, Ugo De Giorgi, Veronica Murianni, Marika Cinausero, Helga Lipari, Teresa Gamba, Orazio Caffo, Davide Bimbatti, Arianna Dri, Alessandra Mosca, Paola Ermacora, Francesca Vignani, Aichi Msaki, Barbara Bonifacio, Valentina Lombardo, Vincenza Conteduca, Giuseppe Fornarini, Pasquale Rescigno
Summary: This study investigated prognostic factors for older patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving androgen receptor pathway inhibitors (ARPIs) treatment. It found that G8 assessment score <= 14 and PSA decline >= 50% were independent factors associated with worse radiographic progression-free survival and overall survival.
