Article
Immunology
Bingxiang Xu, Mingjie Lu, Linlin Yan, Minghui Ge, Yong Ren, Ru Wang, Yongqian Shu, Lin Hou, Hao Guo
Summary: DNA methylation profiles have been identified as potential predictors for responses to immune checkpoint inhibitor treatments due to their stability and ease of measurement, showing high performance in predicting treatment responses at both pan-cancer and specific cancer type levels. Combining DNA methylation profiles with gene expression profiles may further enhance the prediction of responses to ICI treatments.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Giandomenico Roviello, Luigi Francesco Iannone, Melissa Bersanelli, Enrico Mini, Martina Catalano
Summary: Immunotherapy has revolutionized cancer treatment, but reliable biomarkers for predicting treatment response are still unknown. Recent studies suggest that the gut microbiota may play a role in modulating the efficacy and toxicity of immunotherapy drugs.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Guiyuan Chen, Xiangxia Li, Rui Li, Kecheng Wu, Zhouhang Lei, Ruike Dai, Kyle Roche, Andrew Z. Wang, Yuanzeng Min
Summary: Researchers hypothesized that treating cancer cells with ultrahigh doses of chemotherapeutics in vitro could artificially enhance the immunogenicity, thereby improving chemoimmunotherapy.
Review
Medicine, Research & Experimental
Hajar Alemohammad, Basira Najafzadeh, Zahra Asadzadeh, Amir Baghbanzadeh, Farid Ghorbaninezhad, Arezoo Najafzadeh, Hossein Safarpour, Renato Bernardini, Oronzo Brunetti, Margherita Sonnessa, Rossella Fasano, Nicola Silvestris, Behzad Baradaran
Summary: The growth and development of cancer are directly correlated to the suppression of the immune system, with immune checkpoints playing a key role in inhibiting anti-tumor immune responses. Up-regulation of inhibitory immune checkpoints on immune cells during tumor progression suppresses anti-tumor immune responses and promotes immune escape. Targeting inhibitory immune checkpoints through antibodies or miRNAs is a promising therapeutic strategy, and immune checkpoint inhibitors have shown favorable results in enhancing immune cell-induced antitumor responses.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Oncology
Yefang Lao, Daoming Shen, Weili Zhang, Rui He, Min Jiang
Summary: Immune checkpoint inhibitors are an important strategy in cancer therapy, but some patients develop resistance to these inhibitors. Understanding the mechanisms of antitumor action and drug resistance is crucial to narrow down the population of resistant patients. This review discusses the antitumor action sites and mechanisms of different types of immune checkpoint inhibitors, as well as proposes current and future solutions for resistance.
Review
Oncology
Carly C. Barron, Isabella Stefanova, Yevin Cha, Karam Elsolh, Arman Zereshkian, Nessma Gaafour, Elaine McWhirter
Summary: Immune-related adverse events (irAEs) are toxicities resulting from use of immune checkpoint inhibitors (ICIs). These side effects persist in some patients despite withholding therapy and using immunosuppressive and immune-modulating agents. Little is known about chronic irAEs and they are felt to be rare.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Anne Zaremba, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Claudia Pfoehler, Michael Weichenthal, Patrick Terheyden, Andrea Forschner, Ulrike Leiter, Jens Ulrich, Jochen Utikal, Julia Welzel, Martin Kaatz, Christoffer Gebhardt, Rudolf Herbst, Anca Sindrilaru, Edgar Dippel, Michael Sachse, Frank Meiss, Lucie Heinzerling, Sebastian Haferkamp, Carsten Weishaupt, Harald Loeffler, Sophia Kreft, Klaus Griewank, Elisabeth Livingstone, Dirk Schadendorf, Selma Ugurel, Lisa Zimmer
Summary: This study analyzed the impact of NRAS gene mutations on melanoma patients treated with immune checkpoint inhibitors. The results showed that NRAS mutations were not significantly correlated with patients' survival and treatment response, and had no correlation with the expression of the T-cell immune checkpoint molecule PD-L1.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Pharmacology & Pharmacy
Yun Tian, Zhenzhu Liu, Jianbo Wang, Linan Li, Fuli Wang, Zheng Zhu, Xuejian Wang
Summary: Urologic cancers, such as kidney, bladder, and prostate cancer, have a growing incidence and cause a significant number of deaths worldwide. Immunotherapy, including immunological checkpoint blockade, non-specific activation of the immune system, adoptive cell therapy, and tumor vaccine, shows promise but faces challenges in terms of toxicities and response rates. Nanomaterial-based platforms offer solutions by combining nanotechnology with immunotherapy, leading to precision medicine, improved efficacy, and reduced toxicities in urologic cancer treatment.
Article
Oncology
A. Bessede, A. Marabelle, J. P. Guegan, F. X. Danlos, S. Cousin, F. Peyraud, N. Chaput, M. Spalato, G. Roubaud, M. Cabart, M. Khettab, A. Chaibi, C. Rey, I Nafia, F. X. Mahon, J. C. Soria, A. Italiano
Summary: The study reveals that acetaminophen (APAP) may suppress antitumor immunity and impact the efficacy of immunotherapy in cancer patients.
ANNALS OF ONCOLOGY
(2022)
Article
Immunology
Ying Wang, Mengxue Yang, Mingyang Tao, Peipei Liu, Cheng Kong, Hao Li, Yingmei Chen, Xudong Yin, Xuebing Yan
Summary: The use of corticosteroids for cancer-related indications in lung cancer patients receiving ICI treatment is associated with poorer prognosis, as demonstrated by meta-analysis and retrospective analysis. Subgroup analysis focusing on non-small cell lung cancer (NSCLC) showed similar results, highlighting the importance of careful selection of corticosteroid-treated patients for ICI therapy in personalized clinical management.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Oncology
Huizhen Liu, Lixin Sun, Jing Lian, Lixia Wang, Yanfeng Xi, Guohai Zhao, Jiahong Wang, Xiaoyu Lan, Haiyan Du, Wenxia Yan, Peng Bu, Ping Wang, Anna Moore, Hongwei Zhao
Summary: This study investigated the consistency of PD-L1 and MMR expression in primary and matched recurrent/metastatic lesions from patients with cervical cancer. The results showed that PD-L1 expression had lower consistency, while MMR expression had high consistency between primary and metastatic lesions. These findings have important implications for guiding immunotherapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Genetics & Heredity
Subramaniam Jayanthi, Michael T. McCoy, Jean Lud Cadet
Summary: Methamphetamine-use disorder is a serious condition that can lead to long-term changes in the brain and gene expression, highlighting the importance of researching the underlying mechanisms.
Review
Biochemistry & Molecular Biology
Areti Strati, Panagiota Economopoulou, Evi Lianidou, Amanda Psyrri
Summary: The approval of monoclonal antibodies against PD-L1 and PD1 has revolutionized cancer treatment, but the occurrence of irAEs highlights the need for biomarker analysis with strong predictive value. Liquid biopsy is an important tool for clinical oncologists to monitor and adjust therapy, and CTCs expressing PD-L1 can serve as a clinically useful and non-invasive method to assess PD-L1 status in real-time.
Review
Immunology
Chen Shen, Mei Li, Yujuan Duan, Xin Jiang, Xiaoming Hou, Fulai Xue, Yinan Zhang, Yao Luo
Summary: Hepatocellular carcinoma (HCC) is a common liver cancer with poor prognosis and increasing incidence globally. Immunotherapy has been considered as an ideal approach for HCC treatment and is changing patient management. However, immunotherapy resistance hinders the effectiveness of current therapies for some HCC patients. Recent studies have shown that histone deacetylase inhibitors (HDACis) can enhance the efficacy of immunotherapy in various tumors, including HCC. This review discusses the current understanding and recent advances in immunotherapy-based and HDACi-based treatments for HCC, highlighting the synergistic effects of these therapies and efforts to translate this knowledge into clinical benefits. Additionally, the potential of nano-based drug delivery systems (NDDS) as a novel strategy to enhance HCC treatment is explored.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Andrea Palicelli, Stefania Croci, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Magda Zanelli, Alcides Chaux, Sofia Canete-Portillo, Maria Paola Bonasoni, Alessandra Soriano, Stefano Ascani, Maurizio Zizzo, Carolina Castro Ruiz, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe Carrieri, Luigi Cormio, Daniel M. Berney, Jatin Gandhi, Davide Nicoli, Enrico Farnetti, Giacomo Santandrea, Martina Bonacini
Summary: Epigenetic alterations impact the expression of PD-L1 in prostate cancer, with DNA methylation and miRNAs being key factors. Histone modifiers and epigenetic drugs can reverse these alterations. miRNAs can regulate PD-L1 post-transcriptionally, offering potential clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Beatrice Noce, Elisabetta Di Bello, Clemens Zwergel, Rossella Fioravanti, Sergio Valente, Dante Rotili, Andrea Masotti, Mohammad Salik Zeya Ansari, Daniela Trisciuoglio, Alokta Chakrabarti, Christophe Romier, Dina Robaa, Wolfgang Sippl, Manfred Jung, Cecile Haeberli, Jennifer Keiser, Antonello Mai
Summary: Schistosoma mansoni HDAC8 is a reliable target for combating schistosomiasis, but most inhibitors lack selectivity over human deacetylases and have low or no activity against the parasite. In this study, a small library of HDAC inhibitors from the lab was tested for their in vitro enzyme and biological activity. These inhibitors showed submicromolar/nanomolar potency against smHDAC8 and varied selectivity over hHDAC1 and/or hHDAC6. Some compounds exhibited high activity against larval and adult stages of S. mansoni with moderate to no toxicity in human fibroblast cells.
Review
Pharmacology & Pharmacy
Clemens Zwergel, Rossella Fioravanti, Antonello Mai
Summary: Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that, when overexpressed, induces an inhibitory signal causing T cell exhaustion and immune escape in tumors. Immunotherapy targeting the PD-L1 pathway has successfully treated various cancers. Recent advances in understanding the complex biology of PD-L1 have led to the development of small-molecule inhibitors. This review highlights the most promising recent advances in understanding the regulation mechanisms of PD-L1 and the use of small-molecule modulators in combination therapy with other epigenetic chemotherapeutic agents.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Medicinal
Elisabetta Di Bello, Veronica Sian, Giulio Bontempi, Clemens Zwergel, Rossella Fioravanti, Beatrice Noce, Carola Castiello, Stefano Tomassi, Davide Corinti, Daniela Passeri, Roberto Pellicciari, Ciro Mercurio, Mario Varasi, Lucia Altucci, Marco Tripodi, Raffaele Strippoli, Angela Nebbioso, Sergio Valente, Antonello Mai
Summary: After years of research, HDAC inhibitors have been developed and approved by FDA/Chinese FDA for the treatment of cancer and non-cancer diseases. A series of novel compounds have been discovered to be effective anticancer agents, demonstrating selective inhibition of HDACs and inducing cell death and differentiation. These compounds also modulate gene and protein expression related to apoptosis and show potent antiproliferative activity in various cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Aide Negri, Marina Marozzi, Daniela Trisciuoglio, Dante Rotili, Antonello Mai, Federica Rizzi
Summary: Androgen deprivation therapy (ADT) is a common treatment for recurrent prostate cancer (PC), but ADT resistance often occurs leading to lethal metastatic castration-resistant prostate cancer (mCRPC). In this study, the combination of an EZH2 inhibitor with a BET inhibitor showed superior effects in inhibiting cell viability, proliferation, and clonogenic ability, and also reduced the expression of c-myc and NF-kB. These promising results suggest that this combination may be a suitable treatment option for mCRPC by targeting different molecular pathways.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Francesco Fiorentino, Martina Menna, Dante Rotili, Sergio Valente, Antonello Mai
Summary: RNA methylation is a crucial mechanism for regulating gene expression and RNA maturation. METTL3, an RNA methyltransferase, plays a key role in this process by adding a methyl group to N6-adenosine of RNA. Dysregulation of METTL3 can lead to various diseases and viral infections. By studying the correlation between METTL3 and diseases, as well as analyzing the development and mode of action of known METTL3 inhibitors, we can gain a better understanding of the biological functions of this enzyme and potentially develop new therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jujun Zhou, Youchao Deng, Iredia D. Iyamu, John R. Horton, Dan Yu, Taraneh Hajian, Masoud Vedadi, Dante Rotili, Antonello Mai, Robert M. Blumenthal, Xing Zhang, Rong Huang, Xiaodong Cheng
Summary: We modified S-adenosyl-L-methionine (SAM) analogs to discover potent and selective inhibitors of Clostridioides difficile-specific DNA adenine MTase (CamA). Compound 11a, with a 3-phenylpropyl moiety at the adenine N6-amino group and a 3-(cyclohexylmethyl guanidine)-ethyl moiety at the sulfur atom, exhibited higher inhibitory activity against CamA compared to its parental compounds. Our study provides a hybrid approach for generating CamA inhibitors and offers potential chemical agents to investigate the mechanism and therapeutic potential of CamA in C. difficile infection.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Francesco Fiorentino, Alessio Nocentini, Dante Rotili, Claudiu T. Supuran, Antonello Mai
Summary: Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. This study investigated various drugs as potential CA activators and found that phenothiazine-based antipsychotics and tricyclic antidepressants were the most effective at activating hCA VII. These findings provide insights into the pharmacological profiles of clinically employed drugs and may contribute to the development of novel CA activators.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Michele Aventaggiato, Federica Barreca, Laura Vitiello, Simone Vespa, Sergio Valente, Dante Rotili, Antonello Mai, Lavinia Vittoria Lotti, Luigi Sansone, Matteo A. Russo, Mariano Bizzarri, Elisabetta Ferretti, Marco Tafani
Summary: Life on Earth has evolved in the presence of gravity constraint, and any change in gravity has important physiological effects. Our study demonstrates that activation of mitochondrial Sirtuin 3 (SIRT3) can reduce muscle damage caused by microgravity and preserve muscle differentiation. We simulated microgravity on a muscle and cardiac cell line and treated the cells with a newly synthesized SIRT3 activator. The results show that SIRT3 activation reduces microgravity-induced cell death and maintains muscle cell differentiation markers.
Article
Biochemistry & Molecular Biology
Francesco Fiorentino, Antonello Mai, Dante Rotili
Summary: Sirtuins are NAD+-dependent enzymes with multiple functions, including DNA repair, cell survival, metabolism, ROS detoxification, inflammation, cardiac function, and neuronal signaling. The development of sirtuin activators has gained significant interest due to their beneficial effects on health and lifespan. Structural biology has played a crucial role in discovering and characterizing these activators, providing insights into their mechanisms of action and enabling the design of more potent and selective molecules.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Editorial Material
Chemistry, Medicinal
Francesco Fiorentino, Fabrizio Carta, Dante Rotili, Antonello Mai, Claudiu T. Supuran
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Clemens Zwergel, Michele Aventaggiato, Sabrina Garbo, Elisabetta Di Bello, Bruno Fassari, Beatrice Noce, Carola Castiello, Chiara Lambona, Federica Barreca, Dante Rotili, Rossella Fioravanti, Thomas Schmalz, Michael Weyand, Amelie Niedermeier, Marco Tripodi, Gianni Colotti, Clemens Steegborn, Cecilia Battistelli, Marco Tafani, Sergio Valente, Antonello Mai
Summary: The mitochondrial protein SIRT3 plays a role in cancer, metabolism, and hypoxia-related diseases. New 1,4-dihydropyridine compounds, namely 2 and 3, have been discovered and compound 3 is a specific activator of SIRT3. Among a series of related compounds, compound 3c binds and activates SIRT3 the strongest, while compound 3d shows the best effects on enhancing glutamate dehydrogenase activity and deacetylating proteins in breast cancer cells. Compound 3d also exhibits significant anti-cancer effects in both normoxia and hypoxia conditions, reducing cell viability, clonogenicity, and migration ability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Joana Reis, Christoph Gorgulla, Marta Massari, Sara Marchese, Sergio Valente, Beatrice Noce, Lorenzo Basile, Ricarda Toerner, Huel Cox, Thibault Viennet, Moon Hee Yang, Melissa M. Ronan, Matthew G. Rees, Jennifer A. Roth, Lucia Capasso, Angela Nebbioso, Lucia Altucci, Antonello Mai, Haribabu Arthanari, Andrea Mattevi
Summary: In this study, the authors validate inhibitors for human NOX enzymes using computational and experimental methods, opening avenues for cancer drug development and research in redox biology.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Federica Barreca, Michele Aventaggiato, Laura Vitiello, Luigi Sansone, Matteo Antonio Russo, Antonello Mai, Sergio Valente, Marco Tafani
Summary: This study suggests that activation of SIRT5 and reduction in Pi could be a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy, leading to the accumulation of ROS.