Review
Oncology
Maryland Rosenfeld Franklin, Suso Platero, Kamal S. Saini, Giuseppe Curigliano, Steven Anderson
Summary: The field of immuno-oncology has seen significant changes, with a wide range of potential therapies and combinations being evaluated in clinical trials. Successful development of these therapies requires the use of appropriate tools and technologies, such as preclinical models, biomarkers, and efficient clinical trial designs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Evan C. Chen, Helen Gandler, Isidora Tosic, Geoffrey G. Fell, Ashlee Fiore, Olga Pozdnyakova, Daniel J. DeAngelo, Ilene Galinsky, Marlise R. Luskin, Martha Wadleigh, Eric S. Winer, Rebecca Leonard, Kelsey O'Day, Adrienne de Jonge, Donna Neuberg, A. Thomas Look, Richard M. Stone, David A. Frank, Jacqueline S. Garcia
Summary: The study aimed to investigate the safety and biological activity of the MET inhibitor merestinib in combination with the FGFR inhibitor LY2874455 for patients with R/R AML. The results showed that single-agent merestinib at a dose of 80 mg daily was safe and effective, while the combination therapy with LY2874455 may have resistance mechanisms. The study demonstrated that MET and FGFR are biologically active and safely targetable pathways in AML.
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Calogera Claudia Spagnolo, Giuliana Ciappina, Elisa Giovannetti, Andrea Squeri, Barbara Granata, Chiara Lazzari, Giulia Pretelli, Giulia Pasello, Mariacarmela Santarpia
Summary: In recent years, the development of therapeutic agents targeting actionable oncogenic drivers in metastatic non-small cell lung cancer (NSCLC) has increased. Selective inhibitors, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have shown promising results in patients with MET deregulation, specifically exon 14 skipping mutations or MET amplification. This review provides an overview of MET signaling pathways, oncogenic alterations, laboratory techniques for detection, clinical data and ongoing studies on MET inhibitors, resistance mechanisms, and potential strategies for improving outcomes in MET-exon 14-altered NSCLC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Fei Zhang, Ling-Dong Xu, Qian Zhang, Ailian Wang, Xinyuan Yu, Shengduo Liu, Chu Chen, Shiying Wu, Jianping Jin, Aifu Lin, Dante Neculai, Bin Zhao, Xin-Hua Feng, Tingbo Liang, Pinglong Xu, Yao-Wei Huang
Summary: We identified 17 efficient anti-hepatitis E virus (HEV) drugs through high-throughput screening, which showed promising results in vitro and in vivo. These drugs target the proteostasis of the HEV replicase and exhibited superior efficacy compared to conventional antivirals. This study provides insights into the critical host-HEV interactions and lays the foundation for the development of clinically promising antivirals.
JOURNAL OF HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
Nathan D. Winters, Gaurav Bedse, Anastasia A. Astafyev, Toni A. Patrick, Megan Altemus, Amanda J. Morgan, Snigdha Mukerjee, Keenan D. Johnson, Vikrant R. Mahajan, Md Jashim Uddin, Philip J. Kingsley, Samuel W. Centanni, Cody A. Siciliano, David C. Samuels, Lawrence J. Marnett, Danny G. Winder, Sachin Patel
Summary: Alcohol use disorder is associated with significant harm, and pharmacological treatment options are limited. Inhibition of DAGL to reduce 2-AG signaling may be an effective approach to decreasing alcohol consumption across varying severity levels of AUD.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Pharmacology & Pharmacy
Carina Peres, Ana Matos, Liane I. F. Moura, Rita C. Acurcio, Barbara Carreira, Sabina Pozzi, Daniella Vaskovich-Koubi, Ron Kleiner, Ronit Satchi-Fainaro, Helena F. Florindo
Summary: Targeted immunotherapies have revolutionized cancer treatment, but tumor heterogeneity and immunosuppression mechanisms have hindered the success of cancer vaccines. Nanotechnology offers promising solutions, but the selection of appropriate preclinical models is crucial.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Oncology
Elizabeth R. Tucker, Irene Jimenez, Lindi Chen, Angela Bellini, Chiara Gorrini, Elizabeth Calton, Qiong Gao, Harvey Che, Evon Poon, Yann Jamin, Barbara Martins Da Costa, Karen Barker, Sumana Shrestha, J. Ciaran Hutchinson, Simran Dhariwal, Angharad Goodman, Elaine Del Nery, Pierre Gestraud, Jaydutt Bhalshankar, Yasmine Iddir, Elnaz Saberi-Ansari, Alexandra Saint-Charles, Birgit Geoerger, Maria Eugenia Marques Da Costa, Cecile Pierre-Eugene, Isabelle Janoueix-Lerosey, Didier Decaudin, Fariba Nemati, Angel M. Carcaboso, Didier Surdez, Olivier Delattre, Sally L. George, Louis Chesler, Deborah A. Tweddle, Gudrun Schleiermacher
Summary: ALK-activating mutations are present in approximately 10% of neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation ALK inhibitor, is being considered as a treatment for children with ALK-aberrant neuroblastoma. Resistance to single-agent treatment has been reported, and combination therapies with chemotherapy or MDM2 inhibitor are being explored to improve treatment efficacy.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Michelle P. Clark, Thao Huynh, Shringar Rao, Liana Mackiewicz, Hugh Mason, Shahla Romal, Michael D. Stutz, Sang H. Ahn, Linda Earnest, Vitina Sozzi, Margaret Littlejohn, Bang M. Tran, Norbert Wiedemann, Elizabeth Vincan, Joseph Torresi, Hans J. Netter, Tokameh Mahmoudi, Peter Revill, Marc Pellegrini, Gregor Ebert
Summary: This study demonstrated a clinically viable strategy for potentially eliminating chronic HBV reservoirs in patients by using orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins. The research established a reservoir similar to cccDNA in immunocompetent mice using linearized single genome length HBV DNA and confirmed the clinical relevance of the results using primary human liver organoid models.
CELL DEATH & DISEASE
(2021)
Review
Oncology
Wout Devlies, Florian Handle, Gaetan Devos, Steven Joniau, Frank Claessens
Summary: This review investigates the existing methods to study treatment resistance to androgen receptor targeted therapies in prostate cancer, including the role of preclinical models and understanding of resistance mechanisms. Understanding resistance will greatly improve insights into tumor pathophysiology and future treatment strategies in prostate cancer.
Review
Pharmacology & Pharmacy
Bruno Toson, Isadora S. Fortes, Rafael Roesler, Saulo F. Andrade
Summary: This article reviews the application of Akt inhibitors in pediatric cancers. The study demonstrates the impact of Akt inhibition on tumorigenesis and suggests targeting the PI3K/Akt/mTOR signaling pathway as an effective approach for treating pediatric tumors.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Oncology
Elisabeth von Guggenberg, Petra Kolenc, Christof Rottenburger, Renata Mikolajczak, Alicja Hubalewska-Dydejczyk
Summary: Peptide analogs derived from gastrin show promise in improving tumor imaging and treatment by specifically binding to the cholecystokinin-2 receptor expressed on tumor cells. Recent developments include modifications to safely deliver radiation to tumor sites, leading to the introduction of new radiolabeled peptide analogs for cancer imaging and therapy. Ongoing clinical trials suggest a reasonable clinical applicability for CCK2R-targeted radiopharmaceuticals, especially in advanced medullary thyroid cancer.
Review
Biotechnology & Applied Microbiology
E. Elizabeth Patton, Leonard I. Zon, David M. Langenau
Summary: Zebrafish have become a valuable tool in drug discovery, particularly in screening, disease modeling, and toxicity assays. Recent advances in gene modification technologies and xenografts have enabled personalized treatments and rapid drug discovery platforms using zebrafish models. The unique features of zebrafish make them an important model organism for maximizing potential in medical discoveries.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Article
Oncology
Marjolein C. Stip, Mitchell Evers, Maaike Nederend, Chilam Chan, Karli R. Reiding, Mirjam J. Damen, Albert J. R. Heck, Sofia Koustoulidou, Ruud Ramakers, Gerard C. Krijger, Remmert de Roos, Edouard Souteyrand, Annelisa M. Cornel, Miranda P. Dierselhuis, Marco Jansen, Mark de Boer, Thomas Valerius, Geert van Tetering, Jeanette H. W. Leusen, Friederike Meyer-Wentrup
Summary: Researchers engineered an antibody called IgA3.0 ch14.18, which shows promise as a new therapy for neuroblastoma. The antibody has a longer half-life, increased protein stability, and potent tumor-killing abilities.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Richard Riedel, Jana Fassunke, Hannah L. Tumbrink, Andreas H. Scheel, Carina Heydt, Lena Hieggelke, Matthias Scheffler, Alena Heimsoeth, Lucia Nogova, Sebastian Michels, Jan-Phillip Weber, Rieke N. Fischer, Anna Eisert, Theresa Westphal, Diana Schaufler, Janna Siemanowski, Michaela A. Ihle, Svenja Wagener-Ryczek, Roberta Castiglione, Roberto Pappesch, Jan Rehker, Jessica Juergens, Erich Stoelben, Anne Bunck, Carsten Kobe, Sabine Merkelbach-Bruse, Martin L. Sos, Reinhard Buettner, Juergen Wolf
Summary: This study describes the resistance mechanisms to MET inhibition in MET-dependent non-small cell lung cancer patients, including MET exon 14 skipping mutation, MET amplification, and MET fusion. Analysis of patient samples revealed on-and off-target resistance mechanisms, such as KRAS mutations and HER2 amplification. Switching between different types of kinase inhibitors can lead to repeated responses in some patients.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Seung Yeon Oh, You Won Lee, Eun Ji Lee, Jae Hwan Kim, YoungJoon Park, Seong Gu Heo, Mi Ra Yu, Min Hee Hong, John DaSilva, Christopher Daly, Byoung Chul Cho, Sun Min Lim, Mi Ran Yun
Summary: REGN5093-M114, a novel antibody-drug conjugate targeting MET, exhibits significant antitumor activity in EGFR-mutated non-small cell lung cancer (NSCLC) patients. Regardless of MET gene copy number, MET-overexpressed TKI-naive EGFR-mutant NSCLC cells respond to REGN5093-M114 treatment. REGN5093-M114 potently reduces tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation.
CLINICAL CANCER RESEARCH
(2023)