Review
Oncology
Rebecca Adams, Gabriel Osborn, Bipashna Mukhia, Roman Laddach, Zena Willsmore, Alicia Chenoweth, Jenny L. C. Geh, Alastair D. MacKenzie Ross, Ciaran Healy, Linda Barber, Sophia Tsoka, Victoria Sanz-Moreno, Katie E. Lacy, Sophia N. Karagiannis
Summary: The application of monoclonal antibodies in the treatment of melanoma has significantly improved clinical management over the last decade, but more than half of patients do not benefit from treatment. Targeting tumor-associated macrophages (TAMs) and exploring new treatment strategies based on their diversity and plasticity hold promise for enhancing treatment success.
Article
Oncology
Simone M. Goldinger, Kristina Buder-Bakhaya, Serigne N. Lo, Andrea Forschner, Meredith McKean, Lisa Zimmer, Chloe Khoo, Reinhard Dummer, Zeynep Eroglu, Elizabeth I. Buchbinder, Paolo A. Ascierto, Ralf Gutzmer, Elisa A. Rozeman, Christoph Hoeller, Douglas B. Johnson, Anja Gesierich, Peter Koelblinger, Naima Bennannoune, Justine Cohen, Katharina C. Kaehler, Melissa A. Wilson, Jonathan Cebon, Victoria Atkinson, Jessica L. Smith, Olivier Michielin, Georgina Long, Jessica C. Hassel, Benjamin Weide, Lauren E. Haydu, Dirk Schadendorf, Grant McArthur, Patrick A. Ott, Christian Blank, Caroline Robert, Ryan Sullivan, Axel Hauschild, Matteo S. Carlino, Claus Garbe, Michael A. Davies, Alexander M. Menzies
Summary: Chemotherapy has limited activity in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although the activity varies among different chemotherapy regimens.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Oncology
Dhananj ay Yadav, Minseok Kwak, Pallavi Singh Chauhan, Nidhi Puranik, Peter C. W. Lee, Jun-O Jin
Summary: Cancer is the second leading cause of death worldwide. Traditional approaches like surgery, chemotherapy, and radiotherapy have been commonly used for cancer treatment. Cancer immunotherapy, a novel therapeutic modality, boosts the immune responses of patients against malignancy. Recent advances in nanotechnology have facilitated the development of successful and efficient anticancer drug systems based on nanoparticles.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Simon Heller, Sarah Glaeske, Katja Gluske, Juliane Paul, Annika Boehme, Andreas Janzer, Helge Gottfried Roider, Anna Montebaur, Barbara Nicke, Ralf Lesche, Oliver von Ahsen, Oliver Politz, Ningshu Liu, Matyas Gorjanacz
Summary: The study evaluated the effects of the PI3K inhibitor copanlisib on immune cells and tumor growth, and found that combining it with immune checkpoint inhibitors enhances anti-tumor efficacy.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Sunanda Singh, Hector J. J. Gomez, Shreya Thakkar, Samara P. P. Singh, Ashutosh S. S. Parihar
Summary: Anti-neoplastic agents for cancer treatment employ various mechanisms and when combined can effectively inhibit cancer growth. However, the development of acquired drug resistance often renders these agents ineffective. This study identifies at least 24 different anti-neoplastic agents that use the STAT3 signaling pathway to develop therapeutic resistance. Targeting STAT3 in combination with existing agents may be a successful strategy to prevent or overcome drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Multidisciplinary
Salma B. Abdelbaky, Mayar Tarek Ibrahim, Hebatallah Samy, Menatalla Mohamed, Hebatallah Mohamed, Mahmoud Mustafa, Moustafa M. Abdelaziz, M. Laird Forrest, Islam A. Khalil
Summary: Cancer immunotherapy has shown promise in eradicating cancer cells and overcoming multidrug resistance with fewer side effects compared to traditional cytotoxic therapies, utilizing agents such as checkpoint inhibitors and monoclonal antibodies to help immune cells target tumor cells. However, concerns remain around off-target side effects and poor pharmacokinetics in immunotherapeutics. Nanomedicine offers potential solutions by improving drug delivery, release control, and pharmacokinetic profiles, enhancing therapeutic outcomes and minimizing side effects.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Biochemistry & Molecular Biology
Ivana De Risi, Angela Monica Sciacovelli, Michele Guida
Summary: Immune checkpoint inhibition (ICI) has significantly improved the survival of patients with metastatic melanoma (MM), but it also comes with new and sometimes irreversible toxicities. There is currently no consensus on the optimal duration of ICI therapy, and controlled prospective studies are needed.
Article
Oncology
Ryan C. Augustin, Sarah Newman, Aofei Li, Marion Joy, Maureen Lyons, Mary P. Pham, Peter Lucas, Katelyn Smith, Cindy Sander, Brian Isett, Diwakar Davar, Yana G. Najjar, Hassane M. Zarour, John M. Kirkwood, Jason John Luke, Riyue Bao
Summary: In this study, we characterized acral melanoma (AM) and investigated its response to immune checkpoint inhibitors (ICIs). We found differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME) of AM, which may contribute to its poor response to ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Julian Steininger, Frank Friedrich Gellrich, Alexander Schulz, Dana Westphal, Stefan Beissert, Friedegund Meier
Summary: Malignant melanoma is a highly aggressive and metastatic skin cancer, with immunotherapy and targeted therapy showing significant improvement in treatment outcomes by enhancing immune responses and inhibiting abnormal cell growth.
Article
Oncology
Naisheng Zheng, Tingting Wang, Qin Luo, Yi Liu, Junyao Yang, Yunlan Zhou, Guohua Xie, Yanhui Ma, Xiangliang Yuan, Lisong Shen
Summary: M2-like tumor-associated macrophages undermine immune checkpoint blockade therapy by secreting exosomes that decrease tumor immunogenicity through downregulating MHC-I expression. Sensitizing therapy efficacy can be achieved by enhancing ATPase activity of BiP using ApoE ligand EZ-482 to boost tumor immunogenicity. Therefore, ApoE may serve as a predictive factor and potential therapeutic target for ICB resistance in M2-enriched cancer patients.
Article
Immunology
Vera Petrova, Christopher Groth, Rebekka Bitsch, Ihor Arkhypov, Sonja C. S. Simon, Svetlana Hetjens, Verena Mueller, Jochen Utikal, Viktor Umansky
Summary: This study investigated the dynamic changes in immunosuppressive pattern and activity of myeloid-derived suppressor cells (MDSC) in melanoma patients treated with immune checkpoint inhibitors (ICI). It was found that non-responders had higher frequency and immunosuppressive activity of MDSC compared to responders. Additionally, non-responders had higher concentrations of IL-6 and IL-8 before therapy and after the first ICI application compared to responders.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Olivier J. van Not, Melissa M. de Meza, Alfons J. M. van den Eertwegh, John B. Haanen, Christian U. Blank, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Jesper van Breeschoten, Jan-Willem B. de Groot, Geke A. P. Hospers, Rawa K. Ismail, Ellen Kapiteijn, Djura Piersma, Roos S. van Rijn, Marion A. M. Stevense-den Boer, Astrid A. M. van der Veldt, Gerard Vreugdenhil, Han J. Bonenkamp, Marye J. Boers-Sonderen, Willeke A. M. Blokx, Michel W. J. M. Wouters, Karijn P. M. Suijkerbuijk
Summary: This study reveals the lower effectiveness of immune checkpoint inhibitors in patients with acral melanoma compared to cutaneous melanoma, with lower response rates, progression-free survival, and overall survival.
EUROPEAN JOURNAL OF CANCER
(2022)
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
Medicine, Research & Experimental
Qing Wang, Xindi Zhang, Weijun Wei, Min Cao
Summary: Despite advances in cancer treatment, lung cancer remains a leading cause of cancer mortality. Immunotherapies using immune checkpoint inhibitors have shown promise in treating lung cancer. ImmunoPET, utilizing radiolabeled monoclonal antibodies or antibody derivatives as tracers, offers advantages over traditional PET imaging in lung cancer detection, diagnosis, staging, risk stratification, treatment guidance, and recurrence monitoring. ImmunoPET holds potential for patient stratification and response evaluation in immunotherapy. This review summarizes the value of immunoPET in imaging lung cancers and optimizing immunotherapy in NSCLC.
MOLECULAR PHARMACEUTICS
(2022)
Article
Oncology
Cheryl P. Bruijnen, Jose J. Koldenhof, Rik J. Verheijden, Frederiek van den Bos, Marielle H. Emmelot-Vonk, Petronella O. Witteveen, Karijn P. M. Suijkerbuijk
Summary: The study found that while frailty does not seem to be related to the occurrence of severe irAEs, it is an indicator of adverse outcomes related to irAEs, such as hospitalization.
Article
Biochemistry & Molecular Biology
Gianni Colotti, Cristina Maria Failla, Pedro Miguel Lacal, Mariangela Ungarelli, Federica Ruffini, Patrizio Di Micco, Angela Orecchia, Veronica Morea
Summary: NRP-1 is a semaphorin receptor involved in neuron guidance and a co-receptor for certain VEGF isoforms, playing a critical role in angiogenesis and endothelial cell adhesion. Additionally, the interaction between NRP-1 and sVEGFR-1 has been investigated, with potential implications for developing novel anti-angiogenic compounds.
Article
Oncology
Sofia Verkhovskaia, Francesca Romana Di Pietro, Simona Mastroeni, Maria Luigia Carbone, Damiano Abeni, Roberto Morese, Francesca Maria Morelli, Stefania D'Atri, Paolo Marchetti, Federica De Galitiis, Cristina Maria Failla, Cristina Fortes
Summary: The study found that the onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome and an independent predictor factor for longer duration of clinical benefits in patients treated with immune checkpoint inhibitors.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Lucia Lisi, Pedro Miguel Lacal, Maria Martire, Pierluigi Navarra, Grazia Graziani
Summary: Immune checkpoint inhibitors have been investigated as an important approach for cancer immunotherapy, but combination therapy may lead to increased immune-related adverse events. The recent development of anti-CTLA-4 probodies and bispecific molecules targeting both CTLA-4 and PD-1 is considered a potential solution to overcome this drawback.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Grazia Raffaella Tundo, Diego Sbardella, Francesco Oddone, Giuseppe Grasso, Stefano Marini, Maria Grazia Atzori, Anna Maria Santoro, Danilo Milardi, Francesco Bellia, Gabriele Macari, Grazia Graziani, Fabio Polticelli, Paolo Cascio, Mariacristina Parravano, Massimo Coletta
Summary: Carfilzomib has been found to target Insulin-Degrading Enzyme (IDE) in vitro, which has interactions with proteasomes in cells. The inhibitory effect of Carfilzomib on IDE is 10-fold lower than on 20S proteasomes. Additionally, the interaction of IDE with 20S enhances the inhibitory power of Carfilzomib on proteasomes. Silencing the IDE gene significantly reduces the cytotoxicity of Carfilzomib in rMC1 cells.
Article
Dermatology
Mario Picozza, Cristina Cristofoletti, Antonella Bresin, Martina Fioretti, Manolo Sambucci, Enrico Scala, Alessandro Monopoli, Maria Cantonetti, Maria Antonietta Pilla, Maria Pina Accetturi, Giovanna Borsellino, Stefania D'Atri, Elisabetta Caprini, Giandomenico Russo, Maria Grazia Narducci
Summary: Sezary syndrome (SS) is a rare and aggressive variant of cutaneous T-cell lymphoma. This study investigated the expression and function of immune checkpoint molecule CD39 in a large cohort of SS patients and found that the expression level of CD39 is controlled by a genetic variation. Higher expression of CD39 was associated with a better prognosis in SS patients. Inhibition of CD39 enhanced SS cell viability and IL-2 production, suggesting caution in the use of therapeutic inhibitors of CD39 for SS treatment.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Review
Pharmacology & Pharmacy
Claudia Ceci, Pedro Miguel Lacal, Grazia Graziani
Summary: Antibody-drug conjugates (ADCs) are a new group of anticancer agents that combine the selectivity of monoclonal antibodies with the cell killing properties of chemotherapeutic agents. However, the development of ADCs faces challenges such as low tumor selectivity, premature release of drugs, and tumor resistance mechanisms. The design of inert antibodies and the discovery of innovative targets and drugs have led to the development of next-generation ADCs with improved therapeutic properties.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Diego Sbardella, Grazia Raffaella Tundo, Alice Mecchia, Camilla Palumbo, Maria Grazia Atzori, Lauretta Levati, Alessandra Boccaccini, Anna Maria Caccuri, Paolo Cascio, Pedro Miguel Lacal, Grazia Graziani, Monica Varano, Massimiliano Coletta, Mariacristina Parravano
Summary: This study uncovers a novel pathway of Muller glia (MG) activation by high glucose, which is regulated by a calcium-dependent calmodulin kinase II (CamKII)-proteasome axis. Inhibition of CamKII and proteasome prevents the pro-inflammatory program induced by high glucose.
CELL AND BIOSCIENCE
(2022)
Article
Oncology
Lauretta Levati, Cristian Bassi, Simona Mastroeni, Laura Lupini, Gian Carlo Antonini Cappellini, Laura Bonmassar, Ester Alvino, Simona Caporali, Pedro Miguel Lacal, Maria Grazia Narducci, Ivan Molineris, Federica De Galitiis, Massimo Negrini, Giandomenico Russo, Stefania D'Atri
Summary: The study investigated whether circulating miRNAs could serve as biomarkers for clinical outcomes in patients receiving targeted therapy. The results suggest that circulating miR-1246 and miR-485-3p could be valuable biomarkers for identifying melanoma patients most likely to be resistant to targeted therapy or with a poor prognosis.
Article
Biochemistry & Molecular Biology
Claudio Tabolacci, Deborah Giordano, Stefania Rossi, Martina Cordella, Daniela D'Arcangelo, Federica Moschella, Stefania D'Atri, Mauro Biffoni, Angelo Facchiano, Francesco Facchiano
Summary: The study identified DLD as a potential target for overcoming vemurafenib resistance in melanoma cells, through proteomic and structural investigations on resistant sublines.
Review
Pharmacology & Pharmacy
Grazia R. Tundo, Paolo Cascio, Danilo Milardi, Anna Maria Santoro, Grazia Graziani, Pedro Miguel Lacal, Alessio Bocedi, Francesco Oddone, Mariacristina Parravano, Andrea Coletta, Massimo Coletta, Diego Sbardella
Summary: The immunoproteasome, initially discovered for its role in MHC class I antigen processing and immune system modulation, has been found to have additional functions unrelated to antigen presentation. Its expression and activity alterations are important in understanding neuroinflammation dynamics and the pathogenesis of neurological disorders. Furthermore, these new functions suggest the potential of immunoproteasome as a therapeutic target for neurodegeneration. This review provides an overview of the structure-function relationships of immunoproteasome and its observed neuro-modulatory functions.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Maria Grazia Atzori, Claudia Ceci, Federica Ruffini, Manuel Scimeca, Rosella Cicconi, Maurizio Mattei, Pedro Miguel Lacal, Grazia Graziani
Summary: The study indicates that inhibiting the activation of VEGFR-1 by PlGF can effectively restrain the metastatic potential of melanoma, reducing tumor invasiveness and tropism toward bone tissue.
Review
Oncology
Celia Garcia-Chico, Susana Lopez-Ortiz, Saul Penin-Grandes, Jose Pinto-Fraga, Pedro L. Valenzuela, Enzo Emanuele, Claudia Ceci, Grazia Graziani, Carmen Fiuza-Luces, Simone Lista, Alejandro Lucia, Alejandro Santos-Lozano
Summary: The prevalence of breast cancer is increasing and there is a need to investigate the molecular pathways that influence its progression. This review aims to describe the effects of physical exercise on breast cancer hallmarks, which are associated with the development of the disease. Regular physical exercise has positive effects on all major hallmarks of breast cancer and may help counteract its progression.
Article
Pharmacology & Pharmacy
Federica Ruffini, Claudia Ceci, Maria Grazia Atzori, Simona Caporali, Lauretta Levati, Laura Bonmassar, Gian Carlo Antonini Cappellini, Stefania D'Atri, Grazia Graziani, Pedro Miguel Lacal
Summary: The overexpression of PDGF-C and NRP-1 in resistant melanoma cells contributes to their invasive properties. Inhibition of PDGF-C and NRP-1 activation can reduce drug resistance and invasiveness of tumor cells. Furthermore, PDGF-C expression is differentially modulated by BRAFi treatment in responsive and non-responsive melanoma patients, indicating its potential as a therapeutic target for resistant melanoma.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biology
C. Maresca, A. Dello Stritto, C. D'Angelo, E. Petti, A. Rizzo, E. Vertecchi, F. Berardinelli, L. Bonanni, A. Sgura, A. Antoccia, G. Graziani, A. Biroccio, E. Salvati
Summary: PARP1 interacts with TRF1 and modifies its DNA affinity, influencing telomere replication and helicase recruitment. This study uncovers a new role for PARP1 as a surveillant of telomere replication, orchestrating protein dynamics at the replication fork.
COMMUNICATIONS BIOLOGY
(2023)