Review
Health Care Sciences & Services
Evanthia P. Perikleous, Paschalis Steiropoulos, Evangelia Nena, Emmanouil Paraskakis
Summary: Childhood asthma is a common and complex chronic condition in children, and the management of severe asthma remains challenging. The use of biologic agents has shown promise in treating severe childhood asthma, but long-term effects are still unclear. Further research is needed to determine the most effective biologic agents and predictors of treatment response for pediatric patients.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Barry Paul, Cesar Rodriguez, Saad Z. Usmani
Summary: Targeting B cell maturation antigen (BCMA) has emerged as an effective strategy for treating relapsed and refractory myeloma. Several mechanisms, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells and natural killer cells, are being investigated for targeting BCMA. Early phase clinical trials have shown unprecedented response rates in highly refractory myeloma patients, but there are still many questions to be answered.
Review
Oncology
Ajinath Kale, Maciej Lech, Hans-Joachim Anders, Anil Bhanudas Gaikwad
Summary: Lupus nephritis is a severe complication of systemic lupus erythematosus, mainly affecting women of childbearing age. Current treatment options for lupus nephritis have limited effectiveness, but recent drug approvals and clinical trials on novel medications offer hope for improved outcomes. These medications aim to modulate the activity of systemic lupus erythematosus, target non-immune mechanisms of disease progression, or have dual immunosuppressive and antiproteinuric effects, thereby providing more personalized treatment options.
Review
Oncology
Akanksha Sharma, Lauren Singer, Priya Kumthekar
Summary: Metastatic disease to the central nervous system is a serious complication with high mortality rates. Advances in targeted therapy and immunotherapy have led to successful penetration and efficacy within the CNS, improving treatment options for patients. Identifying key targets in tumorigenesis pathway and upcoming trials continue to promise significant progress in managing CNS metastases.
Review
Biochemistry & Molecular Biology
Lifu Long, Zhenjie Yi, Yu Zeng, Zhixiong Liu
Summary: The incidence of brain metastases has been increasing and poses a significant challenge in the medical field. Currently available therapies, such as systemic chemotherapy, targeted therapy, and immunotherapy, face difficulties like drug resistance and low permeability of the blood-brain barrier. Recent research shows that malignant tumor cells can manipulate the brain microenvironment, leading to a pro-tumoral environment. This review compares the characteristics of the brain microenvironment in brain metastases with other sites or primary tumors and evaluates microenvironment-targeted therapies for brain metastases.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Daniel-Clement Osei-Bordom, Sivesh Kamarajah, Niki Christou
Summary: In the clinical management of liver metastasis of colorectal cancer, surgeons and oncologists categorize the metastasis into resectable and non-resectable groups to initiate tailored therapeutics. The combination of targeted therapies and biotherapies around these two entities is being actively explored to determine the ideal conditions for their application to improve patient survival and quality of life.
Article
Cardiac & Cardiovascular Systems
Virginia S. Hahn, Kathleen W. Zhang, Lova Sun, Vivek Narayan, Daniel J. Lenihan, Bonnie Ky
Summary: The growing use of targeted therapies in oncology has led to significant improvements in survival rates, but also presents challenges in managing toxicities associated with long-term treatment. Overlapping signaling pathways may result in systemic toxicities, with cardiovascular toxicities being of particular concern.
CIRCULATION RESEARCH
(2021)
Review
Rheumatology
Giacomo Cozzi, Laura Scagnellato, Mariagrazia Lorenzin, Edoardo Savarino, Fabiana Zingone, Francesca Ometto, Marta Favero, Andrea Doria, Stephan R. Vavricka, Roberta Ramonda
Summary: Spondyloarthritis (SpA) is a group of chronic inflammatory diseases affecting the axial and peripheral joints, tendons, and entheses. Inflammatory bowel disease (IBD) is strongly associated with SpA and has significant impacts on patients' quality of life. Effective treatment requires close collaboration between gastroenterologists and rheumatologists to identify and manage joint and intestinal manifestations, and current drug options for both conditions remain limited.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Review
Pharmacology & Pharmacy
Manyue Zhang, Na Xu, Wenxin Xu, Guixia Ling, Peng Zhang
Summary: With the development of nanotechnology, organelle-targeted nano drug delivery systems have emerged as a potential method to transport drugs specifically to subcellular compartments. Golgi-targeted nano drug delivery systems can alter the morphology of the Golgi apparatus and offer high specificity, low-dose administration, and decreased side effects. This review introduces Golgi-targeted nano drug delivery systems and their applications in disease therapies and diagnosis, including cancer, metastasis, fibrosis, and neurological diseases. It also discusses modifications and strategies to achieve targeting, Golgi-disturbing agents, and special endocytosis for endosomal/lysosomal escape.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Valentina Angerilli, Francesca Galuppini, Gianluca Businello, Luca Dal Santo, Edoardo Savarino, Stefano Realdon, Vincenza Guzzardo, Lorenzo Nicole, Vanni Lazzarin, Sara Lonardi, Fotios Loupakis, Matteo Fassan
Summary: The introduction of precision therapies targeting specific gene mutations in neoplasms is revolutionizing oncology, but resistance mechanisms developed by tumors pose challenges to the effectiveness of these drugs over time. Identifying indicators for monitoring and overcoming drug resistance is crucial. MicroRNAs, as stable molecules easily detectable in tissues and biofluids, are ideal biomarkers for identifying patients with resistance to targeted therapies.
Review
Oncology
Ayse Ece Cali Daylan, Jose Pablo Leone
Summary: Breast cancer patients with brain metastases face a challenging prognosis, but the development of targeted therapies is driving a paradigm shift in the management of this condition, aiming for better efficacy and reduced toxicity.
CLINICAL BREAST CANCER
(2021)
Article
Oncology
C. Villard, M. Habib, C. Nordenvall, P. J. Nilsson, C. Jorns, E. Sparrelid
Summary: Conversion therapy can offer a survival benefit in selected patients, but the majority of patients still cannot undergo liver resection treatment.
Article
Chemistry, Inorganic & Nuclear
Alexander Kastner, Theresa Mendrina, Florian Bachmann, Walter Berger, Bernhard K. Keppler, Petra Heffeter, Christian R. Kowol
Summary: In this study, oxaliplatin(iv)-based complexes were developed as platinum(iv) prodrugs to release aspirin, which has shown antitumor activity against colon cancer. The newly synthesized complex demonstrated increased reduction stability compared to a cisplatin analog and exhibited desired prodrug properties in cell culture. A derivative with albumin-binding properties showed improved pharmacokinetics and tumor accumulation, leading to enhanced antitumor activity and overall survival in tumor-bearing mice.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Review
Oncology
David G. J. Cucchi, Tobias B. Polak, Gert J. Ossenkoppele, Carin A. Uyl-De Groot, Jacqueline Cloos, Sonja Zweegman, Jeroen J. W. M. Janssen
Summary: Precision medicine is increasingly important in treating acute myeloid leukemia (AML). A comprehensive overview of phase II and phase III trials investigating targeted therapies in AML over the past two decades was provided, showing that drugs primarily designed for AML had more success in clinical development compared to repurposed drugs.
Review
Hematology
Sabine Kayser, Mark J. Levis
Summary: Research on the pathogenic mechanisms of AML has made remarkable advances in recent years, especially in the importance of cytogenetic and molecular aberrations. The development of new compounds targeting AML at a molecular level, based on increased understanding of AML pathogenesis facilitated by next-generation sequencing, has turned many hopeful predictions into therapeutic realities.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
J. Randolph Hecht, Kyriakos P. Papadopoulos, Gerald S. Falchook, Manish R. Patel, Jeffrey R. Infante, Raid Aljumaily, Deborah J. Wong, Karen A. Autio, Zev A. Wainberg, Todd M. Bauer, Milind Javle, Shubham Pant, Johanna Bendell, Annie Hung, Navneet Ratti, Peter VanVlasselaer, Rakesh Verma, Joseph Leveque, Sujata Rao, Martin Oft, Aung Naing
Summary: The study demonstrated that pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC patients, with promising efficacy when used in combination therapy.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Oncology
Jeffrey A. How, Amir Jazaeri, Shannon N. Westin, Anil K. Sood, Lois M. Ramondetta, Mingxuan Xu, Abdulrahman Abonofal, Daniel D. Karp, Vivek Subbiah, Bettzy Stephen, Jordi A. Rodon, Fei Yang, Aung Naing
Summary: Treatment of recurrent, unresectable granulosa cell tumor of the ovary can be challenging, and there are currently no reports on the use of immune checkpoint inhibitors in GCT patients. However, a case series showed that some adult-type GCT patients treated with pembrolizumab experienced disease control for over 12 months with low toxicity, suggesting potential clinical benefit in this subset of patients. Further studies are needed to explore the role of immunotherapy in GCT and identify predictors of clinical benefit.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Oncology
Omar Alhalabi, Andrew W. Hahn, Pavlos Msaouel, Alexander Y. Andreev-Drakhlin, Funda Meric-Bernstam, Aung Naing, Sarina Piha-Paul, Janku Filip, Shubham Pant, Timothy A. Yap, David S. Hong, Siqing Fu, Daniel Karp, Erick Campbell, Hung Le, Matthew T. Campbell, Amishi Y. Shah, Nizar M. Tannir, Arlene O. Siefker-Radtke, Jianjun Gao, Jason Roszik, Vivek Subbiah
Summary: The prognosis for patients with metastatic bladder carcinoma (mBC) remains limited, but experimental therapies such as FGFR inhibitors have shown potential efficacy in disease control. Analysis of genetic alterations in TP53, ERBB2, PI3KCA, FGFR3, and ARID1A could help in selecting treatment options for patients.
MOLECULAR CANCER RESEARCH
(2021)
Article
Oncology
Apostolia-Maria Tsimberidou, Henry Hiep Vo, Vivek Subbiah, Filip Janku, Sarina Piha-Paul, Bulent Yilmaz, Jing Gong, Mohammad Faraz Naqvi, Shi-Ming Tu, Matthew Campbell, Funda Meric-Bernstam, Aung Naing
Summary: Lessons learned from the study show that advanced germ cell tumors have poor prognosis, and pembrolizumab, while well tolerated, has limited antitumor activity in these patients. Resistance to immunotherapy in germ cell tumors may be partially attributed to tumor biology and other poor-risk features. Therefore, tumor profiling and innovative clinical trials to identify effective combination regimens are warranted for advanced germ cell tumors.
Article
Oncology
Aung Naing, Fiona Thistlethwaite, Elisabeth G. E. De Vries, Ferry A. L. M. Eskens, Nataliya Uboha, Patrick A. Ott, Patricia LoRusso, Javier Garcia-Corbacho, Valentina Boni, Johanna Bendell, Karen A. Autio, Manreet Randhawa, Greg Durm, Marta Gil-Martin, Mark Stroh, Alison L. Hannah, Hendrik-Tobias Arkenau, Alexander Spira
Summary: Probody therapeutics show potential safety and anti-tumor activity in the treatment of tumors, with low immune-related toxicity and signs of efficacy even in patients with low PD-L1 expression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Ryan C. Augustin, Robert D. Leone, Aung Naing, Lawrence Fong, Riyue Bao, Jason J. Luke
Summary: Evidence supports targeting the adenosine pathway in immuno-oncology, with clinical programs focusing on adenosine receptors and related factors. Intervening in the adenosine pathway can restore immune cell function and inhibit tumor growth.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Editorial Material
Oncology
Shubham Pant, Justin T. Moyers, Aung Naing
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Aung Naing, John D. Powderly, John J. Nemunaitis, Jason J. Luke, Aaron S. Mansfield, Wells A. Messersmith, Solmaz Sahebjam, Patricia M. LoRusso, Ignacio Garrido-Laguna, Lance Leopold, Ryan Geschwindt, Kai Ding, Michael Smith, Jordan D. Berlin
Summary: This study evaluated the combination of Itacitinib with epacadostat or parsaclisib and found limited clinical activity or enhancement of immune activation in the tumor microenvironment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Aung Naing, Alain P. Algazi, Gerald S. Falchook, Benjamin C. Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B. Mettu, Pierre L. Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R. Patel
Summary: This study evaluated the safety and efficacy of the combination therapy of the IDO1 inhibitor epacadostat and the PD-L1 monoclonal antibody durvalumab in patients with advanced solid tumors. The study findings showed that the combination therapy had common adverse events and low objective response rate, and a higher dose of epacadostat was needed for sufficient drug effect.
Article
Oncology
Justin T. Moyers, Roberto Carmagnani Pestana, Jason Roszik, David S. Hong, Aung Naing, Siqing Fu, Sarina Piha-Paul, Timothy A. Yap, Daniel Karp, Jordi Rodon, Andy Livingston, Maria Alejandra Zarzour, Vinod Ravi, Shreyaskumar Patel, Robert S. Benjamin, Joseph Ludwig, Cynthia Herzog, Ravin Ratan, Neeta Somaiah, Anthony Conley, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah
Summary: In this study, the outcomes of patients with ultrarare sarcomas in Phase 1 trials were assessed. The results showed that the median overall survival of ultrarare sarcomas was similar to common sarcomas, but the objective response rate to treatment was higher. Genomic selection played a significant role in identifying molecular subsets likely to benefit from targeted therapy in Phase 1 trials.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Henry Hiep Vo, Siqing Fu, David S. Hong, Daniel D. Karp, Sarina Piha-Paul, Vivek Subbiah, Filip Janku, Aung Naing, Timothy A. Yap, Jordi Rodon, Jaffer A. Ajani, Carrie Cartwright, Amber Johnson, I-Wen Song, Jennifer Beck, Michael Kahle, Graciela M. Nogueras-Gonzalez, Vincent Miller, Calvin Chao, David J. Vining, Donald A. Berry, Funda Meric-Bernstam, Apostolia-Maria Tsimberidou
Summary: The study investigated the challenges faced in conducting the IMPACT2 study in patients with metastatic cancer, revealing the complexity of executing randomized controlled trials in the field of precision oncology for advanced metastatic diseases.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Blessie Elizabeth Nelson, Jason Roszik, Filip Janku, David S. Hong, Shumei Kato, Aung Naing, Sarina Piha-Paul, Siqing Fu, Apostolia Tsimberidou, Maria Cabanillas, Naifa Lamki Busaidy, Milind Javle, Lauren Averett Byers, John V. Heymach, Funda Meric-Bernstam, Vivek Subbiah
Summary: Combined BRAF + MEK inhibition has been approved by FDA for solid tumors with BRAF V600E mutation, except for colorectal cancer. However, besides MAPK-mediated resistance, there are other mechanisms of resistance, such as activation of CRAF, ARAF, MET, P13K/AKT/mTOR pathway. In the VEM-PLUS study, a pooled analysis of four phase one studies was conducted to evaluate the safety and efficacy of vemurafenib monotherapy and combination regimens in advanced solid tumors with BRAF V600 mutations. The results showed that compared to vemurafenib monotherapy, combinations of vemurafenib with targeted therapies or cytotoxic chemotherapy did not significantly improve overall survival (OS) or progression-free survival (PFS) of patients with BRAF V600E-mutant solid tumors.
NPJ PRECISION ONCOLOGY
(2023)
Review
Oncology
Omar Alhalabi, Roman Groisberg, Ralph Zinner, Andrew W. Hahn, Aung Naing, Shizhen Zhang, Apostolia M. Tsimberidou, Jordi Rodon, Siqing Fu, Timothy A. Yap, David S. Hong, Ming Sun, Yunfang Jiang, Shubham Pant, Amishi Y. Shah, Amado Zurita, Nizar M. Tannir, Raghunandan Vikram, Jason Roszik, Funda Meric-Bernstam, Vivek Subbiah
Summary: Pre-clinically, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinums and enhanced paclitaxel-induced cancer cell killing. In a clinical trial, patients with mTOR pathway aberrant tumors were treated with sapanisertib, carboplatin, and paclitaxel. The study showed that the combination therapy had manageable safety and preliminary antitumor activity in advanced malignancies with mTOR pathway alterations.
NPJ PRECISION ONCOLOGY
(2023)
Review
Oncology
Christian Rolfo, Elisa Giovannetti, Pablo Martinez, Shannon McCue, Aung Naing
Summary: Toll-like receptors (TLRs) play a crucial role in the immune system and have the potential to be targeted for cancer therapies. TLRs are involved in the defense against microbes and induce immune responses. By combining TLR agonists with immune checkpoint inhibitors, it is possible to convert cold tumors into hot tumors, improving treatment outcomes. Imiquimod is a TLR7 agonist approved for antiviral and skin cancer treatments, and several other TLR adjuvants are being used in vaccines. Many TLR agonists are currently being developed as monotherapy or in combination with immune checkpoint inhibitors for solid tumors.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Filip Janku, Divya Sakamuri, Shumei Kato, Helen J. Huang, S. Greg Call, Aung Naing, Veronica R. Holley, Sapna P. Patel, Rodabe N. Amaria, Gerald S. Falchook, Sarina A. Piha-Paul, Ralph G. Zinner, Apostolia M. Tsimberidou, David S. Hong, Funda Meric-Bernstam
Summary: The study found that combining vemurafenib with sorafenib or crizotinib could overcome therapeutic resistance in patients with BRAF mutations, and showed good tolerability and encouraging activity. Optional longitudinal collection of plasma to assess dynamic changes in circulating tumor DNA demonstrated the elimination of BRAF-mutant DNA from plasma during therapy (P = .005).