Review
Immunology
Yue Chen, Haoyue Hu, Xianglei Yuan, Xue Fan, Chengda Zhang
Summary: Hepatocellular carcinoma (HCC) is a challenging cancer to treat, but the application of immune checkpoint inhibitors (ICIs) has brought new hope. Combination therapies involving antiangiogenic drugs and ICIs or two ICIs may have a synergistic action and have shown greater efficacy in advanced HCC.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Blanca Cucarull, Anna Tutusaus, Patricia Rider, Tania Hernaez-Alsina, Carlos Cuno, Pablo Garcia de Frutos, Anna Colell, Montserrat Mari, Albert Morales
Summary: Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor prognosis and increasing incidence. Recent advances in systemic treatment options, including tyrosine kinase inhibitors, antiangiogenic antibodies, and immune checkpoint inhibitors, have provided hope for HCC patients. Understanding the specific molecular mechanisms that influence tumor growth and immune control in HCC is crucial for physician decision-making and developing effective treatments.
Review
Cell Biology
Clement Yisai Wang, Stephanie Po Ting Cheung, Ryohichi Sugimura
Summary: Chimeric antigen receptor (CAR) T cells (CAR-T) are a significant personalized anticancer treatment strategy that can bind to tumor-specific antigens and exhibit antitumor abilities. However, the challenges of antigen escape, tumor infiltration, and other toxic side effects restrict the prolonged usage of CAR-T therapies. Engineering immunology, such as stem cell-based CAR-T therapies and CAR-M (macrophage) therapies, have been developed to overcome the limitations of conventional CAR-T therapies. This review highlights the challenges of CAR-T therapies and the potential of engineering immunology for cancer immunotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Roberto Moretto, Daniele Rossini, Aurelie Catteau, Carlotta Antoniotti, Mirella Giordano, Alessandra Boccaccino, Clara Ugolini, Agnese Proietti, Veronica Conca, Alboukadel Kassambara, Filippo Pietrantonio, Lisa Salvatore, Sara Lonardi, Stefano Tamberi, Emiliano Tamburini, Anello Marcello Poma, Jacques Fieschi, Gabriella Fontanini, Gianluca Masi, Jerome Galon, Chiara Cremolini
Summary: The expression of tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) can predict the efficacy of immune-checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Ran Chen, Lei Chen, Chaoqun Wang, Hua Zhu, Lijuan Gu, Yuntao Li, Xiaoxing Xiong, Gang Chen, Zhihong Jian
Summary: This paper discusses the limitations and challenges of CAR-T cell therapy in solid tumors, introduces the latest therapeutic strategies and management decisions to overcome these obstacles, aiming to facilitate the widespread use of CAR-T immunotherapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jia-Shiong Chen, Yi-Chien Hsieh, Cheng-Han Chou, Yi-Hong Wu, Mu-Hsuan Yang, Sz-Hao Chu, Ye-Su Chao, Chia-Nan Chen
Summary: This study investigated the efficacy of the combination therapy of Chidamide with VEGFR tyrosine kinase inhibitors and immune checkpoint inhibitors in murine colon cancer models, revealing a novel tumor microenvironment remodeling mechanism that enhances objective response rate and overall survival by attenuating immunosuppressive cells and restoring T-cell activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Minjiang Chen, Pengfei Ma, Yongchang Zhang, Dong Wang, Zhuang Yu, Yujie Fu, Xiaojing Zhao, Mengzhao Wang, Guanglei Zhuang, Ying Jing
Summary: Our study provides insights into the immune hallmarks associated with response and immune-related adverse events (irAEs) in lung squamous cell carcinoma (LUSC) patients receiving immune checkpoint inhibitors (ICIs). We found specific reprogramming of macrophage, T cells, and tumor cells associated with ICI response and irAEs, elucidated divergent roles of TNF signaling in antitumor immunity and irAEs, and highlighted the significance of TNF expression in irAE development in the LUSC setting.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Sasitorn Yenyuwadee, Konstantinos Aliazis, Qi Wang, Anthos Christofides, Rushil Shah, Nikolaos Patsoukis, Vassiliki A. Boussiotis
Summary: In the past decade, antibody-based and cell-based immunotherapies have revolutionized cancer therapeutics by modulating immune responses against tumors. However, the full potential of immunotherapy has not been reached due to incomplete knowledge of the cellular and molecular mechanisms involved in successful anti-tumor immunity and immune escape.
SEMINARS IN CANCER BIOLOGY
(2022)
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
Immunology
Shanshan Chen, Jingyi Tang, Fen Liu, Wei Li, Ting Yan, Dangang Shangguan, Nong Yang, Dehua Liao
Summary: Non-small cell lung cancer (NSCLC) is commonly driven by mutations in EGFR, KRAS, and ALK genes. Tyrosine kinase inhibitors (TKIs) targeting these genetic drivers have shown better response than chemotherapy, but resistance development remains a challenge. Although immunotherapy has shown promise in other cancers, its efficacy in oncogene-driven NSCLC is limited. The tumor microenvironment (TME) is believed to play a crucial role in the effectiveness of cancer treatment, and TKIs can affect TME. This article discusses the changes in TME in NSCLC after TKI treatments, particularly EGFR-TKIs, to provide insights for new therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Yaping Chen, Hao Huang, Yuan Li, Wenlu Xiao, Yingting Liu, Rongzhang Chen, Yulan Zhu, Xiao Zheng, Changping Wu, Lujun Chen
Summary: Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in cancer treatment, and the combination of ablation and immunotherapy has potential for the treatment of liver metastasis of colorectal cancer (CRC). The expression of TIGIT was up-regulated after microwave ablation (MWA), and the combination of MWA and TIGIT blockade significantly promoted the expansion and functions of CD8(+) tumor-infiltrating lymphocytes (TILs) and reshaped myeloid cells in the tumor microenvironment (TME).
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Deqiang Wang, Xiaofeng Chen, Yian Du, Xiaoqin Li, Leqian Ying, Yi Lu, Bo Shen, Xuan Gao, Xin Yi, Xuefeng Xia, Xinbing Sui, Yongqian Shu
Summary: HER2 mutations may improve the tumor microenvironment to promote immunotherapy. A prospective basket trial is needed to further investigate the impacts of HER2 mutations on immunotherapy outcomes in solid tumors.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Camille Moeckel, Katrina Bakhl, Ilias Georgakopoulos-Soares, Apostolos Zaravinos
Summary: Cancer is a leading cause of death worldwide, and research on potential therapeutics, including immune checkpoint inhibitors (ICIs), has been extensive. Initially, programmed-death ligand-1 was used as a biomarker to predict the effectiveness of ICIs. However, the heterogeneous expression of this biomarker in the tumor microenvironment led to the exploration of tumor mutation burden (TMB).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Daniel R. Principe, Suneel D. Kamath, Murray Korc, Hidayatullah G. Munshi
Summary: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several malignancies but have limited efficacy in certain difficult-to-treat cancer types. Recent research suggests that specific chemotherapy regimens can modify the tumor microenvironment, leading to changes in immune responses. Therefore, the combination of ICIs and cytotoxic chemotherapy shows promise in treating previously unresponsive cancers.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Chemistry, Medicinal
Habib Sadeghi Rad, James Monkman, Majid E. Warkiani, Rahul Ladwa, Ken O'Byrne, Nima Rezaei, Arutha Kulasinghe
Summary: Advances in immunotherapy have provided durable and long-term benefits for certain patients with solid tumors, with a key focus on understanding the immune landscape of the tumor microenvironment to develop effective immunotherapeutic strategies.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Pharmacology & Pharmacy
Chiara Dalle Fratte, Sara Gagno, Rossana Roncato, Jerry Polesel, Martina Zanchetta, Mauro Buzzo, Bianca Posocco, Elena De Mattia, Rachele Borsatti, Fabio Puglisi, Luisa Foltran, Michela Guardascione, Angela Buonadonna, Erika Cecchin, Giuseppe Toffoli
Summary: This study investigated the association between gene activity score and imatinib exposure in GIST patients. The results showed that CYP2D6 plays a major role in imatinib pharmacokinetics, but other factors such as CYP2C8 may also influence the drug's exposure. These findings could help identify patients who are more susceptible to imatinib under- or overexposure for personalized treatment and monitoring strategies.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Maurizio Polano, Luca Bedon, Michele Dal Bo, Roberto Sorio, Michele Bartoletti, Elena De Mattia, Erika Cecchin, Carmela Pisano, Domenica Lorusso, Andrea Alberto Lissoni, Andrea De Censi, Sabrina Chiara Cecere, Paolo Scollo, Sergio Marchini, Laura Arenare, Ugo De Giorgi, Daniela Califano, Elena Biagioli, Paolo Chiodini, Francesco Perrone, Sandro Pignata, Giuseppe Toffoli
Summary: Pharmacogenomics explores how genes affect individual responses to treatment. Utilizing machine learning techniques, this study investigated the relationship between genetic variations and drug-induced toxicities in ovarian cancer patients. The proposed method identified key genetic variations for predicting toxicities and provided valuable data for precision medicine.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Chiara Dalle Fratte, Jerry Polesel, Sara Gagno, Bianca Posocco, Elena De Mattia, Rossana Roncato, Marco Orleni, Fabio Puglisi, Michela Guardascione, Angela Buonadonna, Giuseppe Toffoli, Erika Cecchin
Summary: This study investigated the association between genetic polymorphisms in ABCB1 and ABCG2 and imatinib plasma trough concentration in GIST and CML patients. The results showed a borderline association between the ABCG2 c.421C>A genotype and imatinib plasma trough levels, which was further confirmed in a meta-analysis. However, no significant association was found between ABCB1 polymorphisms and imatinib C-trough.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Martina Zanchetta, Bianca Posocco, Sara Gagno, Ariana Soledad Poetto, Marco Orleni, Giovanni Canil, Michela Guardascione, Fabio Puglisi, Giuseppe Toffoli
Summary: A new LC-MS/MS method was developed for quantifying LENVA in venous DBS samples, characterized by a short run time, volumetric sampling, and extraction of the entire spot to avoid Hct and spot volume effects. The method was validated on two different filter papers according to EMA, FDA, EBF, and IATDMCT guidelines, and showed satisfactory recovery, absence of matrix effect, process efficiency, Hct effect, linearity, precision, accuracy, selectivity, sensitivity, reproducibility, and stability. The method was successfully used to quantify LENVA in DBS samples from hepatocellular carcinoma patients and showed a good correlation with the standard procedure.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Pharmacology & Pharmacy
A. Bignucolo, E. De Mattia, R. Roncato, E. Peruzzi, L. Scarabel, M. D'Andrea, F. Sartor, G. Toffoli, E. Cecchin
Summary: The importance of implementing DPYD pharmacogenetics in clinical practice has been raised and successfully applied in Italy. The development of guidelines, genotyping technology, and research consortia has enhanced the clinical use of DPYD testing. National health policies and recommendations from regulatory agencies have further promoted the application of DPYD testing in drug prescriptions.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Elena De Mattia, Jerry Polesel, Silvia Mezzalira, Elisa Palazzari, Sara Pollesel, Giuseppe Toffoli, Erika Cecchin
Summary: This study aimed to investigate the clinical value of RAS, TP53, BRAF, PIK3CA, and SMAD4 mutations and microsatellite instability (MSI) status as markers for pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients who received preoperative radiation-based therapy. The study found that KRAS mutations were significantly associated with the risk of not achieving pCR after preoperative treatment, especially in patients who did not receive cetuximab. No other markers were associated with pCR. Implementing KRAS mutation testing in clinical practice could improve the management of LARC patients.
Article
Pharmacology & Pharmacy
Giovanni Canil, Marco Orleni, Bianca Posocco, Sara Gagno, Alessia Bignucolo, Marcella Montico, Rossana Roncato, Serena Corsetti, Michele Bartoletti, Giuseppe Toffoli
Summary: Poly (ADP-ribose) polymerase inhibitors (PARPis) are increasingly important in oncology, and their therapeutic drug monitoring (TDM) could benefit patients. This study developed and validated a liquid chromatography-tandem mass spectrometry method for quantifying olaparib, rucaparib, and niraparib in both human plasma and dried blood spot (DBS). The correlation between drug concentrations measured in these two matrices was assessed. Results showed a strong correlation between plasma and DBS for olaparib and niraparib, though further data is needed to establish a robust regression analysis for rucaparib. The study provides a solid foundation for the feasibility of using both plasma and DBS matrices for PARPis TDM.
Article
Medicine, Research & Experimental
Elena Peruzzi, Lorenzo Gerratana, Marcella Montico, Bianca Posocco, Serena Corsetti, Michele Bartoletti, Sara Gagno, Marco Orleni, Elena De Mattia, Massimo Baraldo, Erika Cecchin, Fabio Puglisi, Giuseppe Toffoli, Rossana Roncato
Summary: This study investigates the effect of genetic polymorphisms in ADME genes on the safety profiles of CDKis and identifies several polymorphisms associated with treatment response. These findings are significant for understanding the interindividual variability in CDKis responses.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Rossana Roncato, Elena Peruzzi, Lorenzo Gerratana, Bianca Posocco, Sofia Nuzzo, Marcella Montico, Marco Orleni, Serena Corsetti, Michele Bartoletti, Sara Gagno, Giovanni Canil, Elena De Mattia, Jacopo Angelini, Massimo Baraldo, Fabio Puglisi, Erika Cecchin, Giuseppe Toffoli
Summary: This study investigated the impact of BMI on the safety and efficacy profile of palbociclib in patients with metastatic luminal-like breast cancer. Patients with BMI <25 had higher incidences of hematologic toxicities, dose reduction events, and lower dose intensities, as well as shorter progression-free survival compared to those with BMI ≥25.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Chiara Dalle Fratte, Sara Gagno, Rossana Roncato, Jerry Polesel, Martina Zanchetta, Mauro Buzzo, Bianca Posocco, Elena De Mattia, Rachele Borsatti, Fabio Puglisi, Luisa Foltran, Michela Guardascione, Angela Buonadonna, Erika Cecchin, Giuseppe Toffoli
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Noemi Milan, Palazzari Elisa, Chiara Dalle Fratte, Elena De Mattia, Lucia Scarabel, Michela Zorzi, Rossana Roncato, Elena Peruzzi, Roberto Innocente, Vincenzo Canzonieri, Angela Buonadonna, Renato Cannizzaro, Claudio Belluco, Giuseppe Toffoli, Erika Cecchin
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
JesseJ Swen, Cathelijne H. van der Wouden, Lisanne E. N. Manson, Heshu Abdullah-Koolmees, Kathrin Blagec, Tanja Blagus, Stefan Boehringer, Anne Cambon-Thomsen, Erika Cecchin, Ka-Chun Cheung, Vera H. M. Deneer, Mathilde Dupui, Magnus Ingelman-Sundberg, Siv Jonsson, Candace Joefield-Roka, Katja S. Just, Mats O. Karlsson, Lidija Konta, Rudolf Koopmann, Marjolein Kriek, Thorsten Lehr, Christina Mitropoulou, Emmanuelle Rial-Sebbag, Victoria Rollinson, Rossana Roncato, Matthias Samwald, Elke Schaeffeler, Maria Skokou, Matthias Schwab, Daniela Steinberger, Julia C. Stingl, Roman Tremmel, Richard M. Turner, Mandy H. van Rhenen, Cristina L. Davila Fajardo, Vita Dolzan, George P. Patrinos, Munir Pirmohamed, Gere Sunder-Plassmann, Giuseppe Toffoli, Henk-Jan Guchelaar
Summary: This study assessed the clinical utility of pharmacogenetic testing in patients receiving their first prescription drugs. The results showed that using a pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions, and this strategy was feasible across diverse European healthcare system organizations and settings.
Meeting Abstract
Pharmacology & Pharmacy
Elena Peruzzi, Sofia Nuzzo, Lorenzo Gerratana, Bianca Posocco, Marcella Montico, Marco Orleni, Serena Corsetti, Michele Bartoletti, Elena De Mattia, Noemi Milan, Fabio Puglisi, Giuseppe Toffoli, Erika Cecchin, Rossana Roncato
BRITISH JOURNAL OF PHARMACOLOGY
(2023)