Review
Pharmacology & Pharmacy
Lenka Hruba, Viswanath Das, Marian Hajduch, Petr Dzubak
Summary: Nucleoside-based drugs, widely used in the treatment of various diseases, have been hindered by drug resistance. This review explores the mechanisms of resistance, including changes in membrane transporters, activating kinases, drug elimination strategies, and DNA damage repair mechanisms. The critical analysis in this review points towards novel therapeutic strategies such as targeted therapies, new nucleoside analogs, and synergistic drug combinations to overcome resistance and improve patient outcomes.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Hye-Young Min, Ho-Young Lee
Summary: Molecular targeted therapy has become a fundamental approach in precision medicine for cancer treatment, offering efficient anticancer effects with fewer side effects. However, drug resistance remains a major drawback that needs to be overcome to improve therapeutic efficacy.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Article
Chemistry, Medicinal
Sarah Lazzaro, Mark A. West, Soraya Eatemadpour, Bo Feng, Manthena V. S. Varma, A. David Rodrigues, Csilla Temesszentandrasi-Ambrus, Peter Kovacs-Hajdu, Zsuzsanna Nerada, Zsuzsanna Gaborik, Chester Costales
Summary: This study evaluated the impact of potential IC50 discrepancies between two commonly utilized assay methods (cell-based and vesicle-based) on P-gp. Non-P-gp substrates showed good correlation between the two methods, while IC50s of P-gp substrates were lower in the vesicle assays. IC50s obtained from two independent laboratories using the same method showed good correlation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Ales Sorf, Dimitrios Vagiannis, Fahda Ahmed, Jakub Hofman, Martina Ceckova
Summary: This study found that dabrafenib inhibits ABCG2 and ABCB1 transporters and also inhibits CYP2C8, CYP2C9, CYP3A4, and CYP3A5 enzymes. Additionally, dabrafenib increases the mRNA levels of ABCB1, ABCG2, ABCC1, and CYP3A4. These findings suggest that caution should be taken when using dabrafenib in patients with polypharmacy, but its interactions with other drugs could be utilized to improve the treatment outcome of drug-resistant cancer.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Amandeep Singh Bhatia, Mandeep Kaur Saggi, Sabre Kais
Summary: In drug discovery, evaluating the ADME and toxicity properties of new chemical entities is critical but time-consuming and expensive. Emerging technologies like AI and big data have been used to predict these properties. Quantum computing and machine learning have attracted attention in various fields, including chemistry and biomedicine. Our proposed quantum machine learning framework combines classical and quantum methods to evaluate chemical/drug ADME-Tox properties using the SMILES notation-based string kernel. Large-scale simulations validate the framework, showing that the quantum model outperforms the classical models in predicting outcomes for small molecules with different features.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Pharmacology & Pharmacy
Yik Pui Tsang, Antonio Jesus Lopez Quinones, Leticia Salvador Vieira, Joanne Wang
Summary: The study assessed the interaction between ALK inhibitors and pOCTs, as well as the impact of substrate-dependent inhibition on DDI predictions. Results showed that different inhibitors and substrates have varying effects on pOCTs. This study has important implications for the clinical use of ALK inhibitors and DDI predictions.
Article
Biochemistry & Molecular Biology
B. Dudas, X. Decleves, S. Cisternino, D. Perahia, M. A. Miteva
Summary: This study simulated the transport process of ABCG2 by studying connecting pathways. An additional pocket between the two substrate-binding cavities was discovered, and the role of substrates in the transport process was revealed. The study is of great significance for understanding the complex efflux mechanism of ABCG2.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Masoumeh Divar, Najmeh Edraki, Tahereh Damghani, Fatemeh Moosavi, Maryam Mohabbati, Alireza Alipour, Somayeh Pirhadi, Luciano Saso, Soghra Khabnadideh, Omidreza Firuzi
Summary: Despite advances in therapeutic strategies, cancer remains a leading cause of death. This study synthesized a new series of spiro[indoline-3,2'-quinazoline]-2,4'(3'H)-dione derivatives and evaluated their potential as kinase inhibitors with anti-cancer effects. The most promising compounds exhibited anti-proliferative activity against various cancer cell lines and altered the distribution of cells in the cell cycle. FLT3 kinase was identified as the primary target of these compounds. Compound 5f showed potent inhibitory activity against wild-type FLT3 and its mutant, D835Y. Docking and simulation studies revealed the important interactions of compound 5f with FLT3. These findings suggest that these spiroindoline quinazolinedione compounds could be promising candidates for novel anticancer drugs.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Saleha Anwar, Debarati DasGupta, Alaa Shafie, Fahad A. Alhumaydhi, Suliman A. Alsagaby, Moyad Shahwan, Farah Anjum, Waleed Al Abdulmonem, Sharaf E. Sharaf, Md Imtaiyaz Hassan
Summary: Protein kinase inhibitors are widely used in the treatment of cancer and other diseases. This study focuses on pyruvate dehydrogenase kinase 3 (PDK3) as a potential drug target for cancer therapy. The researchers discovered that tempol is a potent inhibitor of PDK3, and molecular docking and molecular dynamics simulations provided insights into the binding affinity and stability of the PDK3-tempol complex. The study also confirmed the inhibitory action of tempol on PDK3 through binding and inhibition assays.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Review
Pharmacology & Pharmacy
Noor E. Verhagen, Jan B. Koenderink, Nicole M. A. Blijlevens, Jeroen J. W. M. Janssen, Frans G. M. Russel
Summary: Chronic myeloid leukemia (CML) is a type of blood cancer. Targeted therapy has improved the life expectancy of CML patients, but some patients develop resistance to treatment, possibly due to reduced drug concentrations in cells. This review focuses on drug-transporting proteins involved in the distribution of CML treatment drugs.
Review
Oncology
Andrew H. Lipsky, Nicole Lamanna
Summary: Targeted therapies have revolutionized the frontline treatment for CLL, reducing reliance on chemoimmunotherapy. Drugs such as ibrutinib, acalabrutinib, and venetoclax have shown efficacy in oral therapy. This review explores novel therapeutic strategies using these agents in combination, highlighting the importance of patient characteristics and study methodology.
Review
Oncology
Jeffrey W. Fuchs, Brian C. Schulte, Joseph R. Fuchs, Mark Agulnik
Summary: Soft tissue sarcomas are rare malignant tumors derived from mesenchymal cells, and their high morbidity and mortality are often associated with advanced and metastatic disease. Significant progress has been made in the use of targeted therapies for the treatment of soft tissue sarcoma over the past two decades. The ability to study various cellular markers and pathways related to sarcomagenesis has led to the development and approval of multiple novel therapies.
FRONTIERS IN ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xiaoxia Liang, Qian Yang, Pan Wu, Changliang He, Lizi Yin, Funeng Xu, Zhongqiong Yin, Guizhou Yue, Yuanfeng Zou, Lixia Li, Xu Song, Cheng Lv, Wei Zhang, Bo Jing
Summary: This review discusses the development of 30 new inhibitors for cancer therapy in the last five years based on the important roles of protein tyrosine kinase. The synthesis methods of these inhibitors are updated and compared, providing an outlook on the future synthesis of potential PTK inhibitors for anticancer therapy.
BIOORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Skye Montoya, Deborah Soong, Nina Nguyen, Maurizio Affer, Sailasya P. Munamarty, Justin Taylor
Summary: Development of targeted therapies has provided nonchemotherapeutic options for patients, with small molecule kinase inhibitors being a key focus. However, resistance to these therapies may develop, necessitating multiple lines of treatment. Combinations of therapies targeting complimentary pathways may be more effective in overcoming drug resistance.
Review
Biochemistry & Molecular Biology
Lizhuo Zhang, Qingqing Feng, Jiafeng Wang, Zhuo Tan, Qinglin Li, Minghua Ge
Summary: Thyroid cancer is a common endocrine malignant tumor, and surgery, chemotherapy, radiotherapy, and radioactive iodine therapy are the standard treatment modalities. However, multi-tyrosine kinase inhibitors and immune checkpoint inhibitors in combination with tyrosine kinase inhibitors have emerged as novel therapies for controlling the progression of thyroid cancer. This article discusses the molecular basis of thyroid cancer, reviews targeted therapeutic drugs in clinical research, and explores potentially novel molecular therapeutic targets.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Genetics & Heredity
Gloria Ravegnini, Cesar Serrano, Riccardo Ricci, Qianqian Zhang, Irene Terrenato, Agnese Graziosi, Giorgia Valori, Stefania Landolfi, Patrizia Hrelia, Sabrina Angelini
Summary: This study found that miRNA expression in metastatic gastrointestinal stromal tumors has similar characteristics in primary sites and metastases, with the primary origin appearing to be the main determinant of the metastatic miRNA profile.
Article
Oncology
Antonio De Leo, Dario de Biase, Jacopo Lenzi, Giovanna Barbero, Daniela Turchetti, Marco Grillini, Gloria Ravegnini, Sabrina Angelini, Claudio Zamagni, Sara Coluccelli, Giulia Dondi, Pierandrea De Iaco, Anna Myriam Perrone, Giovanni Tallini, Donatella Santini, Claudio Ceccarelli
Summary: The study investigates the impact of ARID1A and CTNNB1/beta-catenin alterations in 125 molecularly classified endometrial carcinomas, showing that ARID1A mutation in NSMP cases is associated with worse outcomes while tumors with ARID1A wild-type and beta-catenin alteration have indolent clinicopathologic features. This study highlights how identifying these alterations in endometrial cancer can help characterize tumor aggressiveness and metastatic potential.
Review
Medicine, General & Internal
Matthew J. Page, Joanne E. McKenzie, Patrick M. Bossuyt, Isabelle Boutron, Tammy C. Hoffmann, Cynthia D. Mulrow, Larissa Shamseer, Jennifer M. Tetzlaff, Elie A. Akl, Sue E. Brennan, Roger Chou, Julie Glanville, Jeremy M. Grimshaw, Asbjorn Hrobjartsson, Manoj M. Lalu, Tianjing Li, Elizabeth W. Loder, Evan Mayo-Wilson, Steve McDonald, Luke A. McGuinness, Lesley A. Stewart, James Thomas, Andrea C. Tricco, Vivian A. Welch, Penny Whiting, David Moher
Summary: The PRISMA statement was designed to help systematic reviewers transparently report the purpose, methods, and findings of their reviews. The updated PRISMA 2020 statement includes new reporting guidance, a 27-item checklist, an abstract checklist, and revised flow diagrams for reviews.
BMJ-BRITISH MEDICAL JOURNAL
(2021)
Article
Medicine, General & Internal
Matthew J. Page, Joanne E. McKenzie, Patrick M. Bossuyt, Isabelle Boutron, Tammy C. Hoffmann, Cynthia D. Mulrow, Larissa Shamseer, Jennifer M. Tetzlaff, Elie A. Akl, Sue E. Brennan, Roger Chou, Julie Glanville, Jeremy M. Grimshaw, Asbjorn Hrobjartsson, Manoj M. Lalu, Tianjing Li, Elizabeth W. Loder, Evan Mayo-Wilson, Steve McDonald, Luke A. McGuinness, Lesley A. Stewart, James Thomas, Andrea C. Tricco, Vivian A. Welch, Penny Whiting, David Moher
Summary: The article introduces PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.
Review
Oncology
Anna Myriam Perrone, Gloria Ravegnini, Stefano Miglietta, Lisa Argnani, Martina Ferioli, Eugenia De Crescenzo, Marco Tesei, Marco Di Stanislao, Giulia Girolimetti, Giuseppe Gasparre, Anna Maria Porcelli, Francesca De Terlizzi, Claudio Zamagni, Alessio Giuseppe Morganti, Pierandrea De Iaco
Summary: Electrochemotherapy (ECT) is an emerging treatment for solid tumors that involves maximizing the action of specific cytotoxic drugs through the tumor-directed delivery of non-ablative electrical pulses. Despite mainly being recommended for palliative care, ECT has the potential to improve patient outcomes by preventing or delaying tumor progression. Additionally, the efficacy of different drugs in ECT, such as cisplatin and bleomycin, should be compared through systematic literature reviews to explore the possibilities of overcoming chemoresistance and improving local control.
Article
Oncology
Anna Myriam Perrone, Martina Ferioli, Lisa Argnani, Francesca De Terlizzi, Cecilia Pirovano, Piero Covarelli, Giulia Dondi, Marco Tesei, Eugenia De Crescenzo, Gloria Ravegnini, Andrea Galuppi, Alessio G. Morganti, Pierandrea De Iaco
Summary: A multicenter prospective observational study found that palliative electrochemotherapy (ECT) can improve quality of life in patients with vulvar cancer (VC), with better results in patients with good clinical response, smaller lesions, and lesions located in the anterior part.
Article
Cell Biology
Irene Soffritti, Maria D'Accolti, Gloria Ravegnini, Maria-Cristina Arcangeletti, Clara Maccari, Flora De Conto, Adriana Calderaro, Elisabetta Caselli
Summary: Viral infections, particularly by HCMV and HHV-6, may play a role in the onset and progression of systemic sclerosis by modulating miRNA expression and causing cell fibrosis, potentially serving as biomarkers for SSc diagnosis, assessment of disease progression, and antifibrotic therapies.
Review
Medicine, General & Internal
Antonio De Leo, Donatella Santini, Claudio Ceccarelli, Giacomo Santandrea, Andrea Palicelli, Giorgia Acquaviva, Federico Chiarucci, Francesca Rosini, Gloria Ravegnini, Annalisa Pession, Daniela Turchetti, Claudio Zamagni, Anna Myriam Perrone, Pierandrea De Iaco, Giovanni Tallini, Dario de Biase
Summary: Ovarian carcinomas are a heterogeneous group of neoplasms with different types and characteristics. The WHO classifies them into five distinct types, each with unique molecular features. Advances in molecular pathology have improved our understanding of ovarian carcinomas and can guide personalized clinical decisions.
Review
Oncology
Gloria Ravegnini, Francesca Gorini, Eugenia De Crescenzo, Antonio De Leo, Dario De Biase, Marco Di Stanislao, Patrizia Hrelia, Sabrina Angelini, Pierandrea De Iaco, Anna Myriam Perrone
Summary: Endometrial cancer is the most common gynecological cancer with challenging diagnostic and prognostic features. miRNAs play an important role in EC but there is currently lack of consensus in studies. Future research needs to explore more diagnostic and prognostic biomarkers and address the challenges in the current classification schemes.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Maria A. Pantaleo, Milena Urbini, Angela Schipani, Margherita Nannini, Valentina Indio, Antonio De Leo, Bruno Vincenzi, Antonella Brunello, Giovanni Grignani, Mariaelena Casagrande, Elena Fumagalli, Elena Conca, Maristella Saponara, Elisa Gruppioni, Annalisa Altimari, Dario De Biase, Giovanni Tallini, Gloria Ravegnini, Daniela Turchetti, Marco Seri, Andrea Ardizzoni, Paola Secchiero, Annalisa Astolfi
Summary: Germline SDHA variants are highly prevalent in SDHA-deficient GIST, and the disease may occur in older adults as well. Genetic testing and surveillance should be conducted for SDHA mutation carriers and their relatives.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
Camelia Alexandra Coada, Giulia Dondi, Gloria Ravegnini, Antonio De Leo, Donatella Santini, Eugenia De Crescenzo, Marco Tesei, Alessandro Bovicelli, Susanna Giunchi, Ada Dormi, Marco Di Stanislao, Alessio G. Morganti, Dario De Biase, Pierandrea De Iaco, Anna Myriam Perrone
Summary: Endometrial cancer is the most common gynecological malignancy. Risk stratification should be based on the integration of histologic, clinical, and molecular parameters.
Article
Biochemistry & Molecular Biology
Gloria Ravegnini, Margherita Nannini, Valentina Indio, Cesar Serrano, Francesca Gorini, Annalisa Astolfi, Aldo Di Vito, Fabiana Morroni, Maria Abbondanza Pantaleo, Patrizia Hrelia, Sabrina Angelini
Summary: GISTs with PDGFRA D842V mutation show differential miRNA expression compared to non-D842V mutated GISTs. Differentially expressed miRNAs mainly target genes involved in the immune response pathways. Additionally, the miRNA-mRNA network reveals the indolent behavior of D842V mutated GISTs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Health Care Sciences & Services
Martina Ruscelli, Thais Maloberti, Angelo Gianluca Corradini, Francesca Rosini, Giulia Querzoli, Marco Grillini, Annalisa Altimari, Elisa Gruppioni, Viviana Sanza, Alessia Costantino, Riccardo Ciudino, Matteo Errani, Alessia Papapietro, Sara Coluccelli, Daniela Turchetti, Martina Ferioli, Susanna Giunchi, Giulia Dondi, Marco Tesei, Gloria Ravegnini, Francesca Abbati, Daniela Rubino, Claudio Zamagni, Emanuela D'Angelo, Pierandrea De Iaco, Donatella Santini, Claudio Ceccarelli, Anna Myriam Perrone, Giovanni Tallini, Dario de Biase, Antonio De Leo
Summary: This study aims to evaluate the impact of integrated molecular and pathologic risk stratification in the clinical practice of endometrial carcinoma (EC). It found that molecular classes and risk groups were correlated with disease-free survival. The study supports the prognostic importance of EC molecular classification and the essential role of histopathologic assessment in patients' management.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Oncology
Camelia Alexandra Coada, Miriam Santoro, Vladislav Zybin, Marco Di Stanislao, Giulia Paolani, Cecilia Modolon, Stella Di Costanzo, Lucia Genovesi, Marco Tesei, Antonio De Leo, Gloria Ravegnini, Dario De Biase, Alessio Giuseppe Morganti, Luigi Lovato, Pierandrea De Iaco, Lidia Strigari, Anna Myriam Perrone
Summary: This study investigated the potential of radiomic features extracted from pre-surgical CT scans to predict disease-free survival (DFS) in endometrial cancer (EC) patients. Machine learning models achieved high sensitivities and specificities in both training and test sets, showing promise for predicting EC recurrence.
Review
Oncology
Federica Medici, Stefania Rizzo, Milly Buwenge, Alessandra Arcelli, Martina Ferioli, Gabriella Macchia, Francesco Deodato, Savino Cilla, Pierandrea De Iaco, Anna Myriam Perrone, Silvia Strolin, Lidia Strigari, Gloria Ravegnini, Alberto Bazzocchi, Alessio G. Morganti
Summary: Sarcopenia is a syndrome characterized by age-related loss of skeletal muscle mass and function, worsens radiation-induced toxicity and prognosis, and has a negative impact on the quality of life. Myosteatosis, a pathological infiltration of muscle tissue by adipose tissue, is correlated with prognosis in cancer patients. Sarcopenic obesity, characterized by large fat mass, is independently associated with higher mortality and worse complications compared to sarcopenia alone. Assessment of sarcopenia is commonly done using CT images. Several studies have shown the negative impact of sarcopenia on overall survival in patients undergoing radiation therapy for various tumors. Further research is needed to find ways to prevent and manage sarcopenia during and after radiation therapy in both adult and pediatric patients.