Article
Oncology
C. Robert, K. D. Lewis, R. Gutzmer, D. Stroyakovskiy, H. Gogas, S. Protsenko, R. P. Pereira, T. Eigentler, P. Rutkowski, L. Demidov, I Caro, H. Forbes, K. Shah, Y. Yan, H. Li, G. A. McArthur, P. A. Ascierto
Summary: The triplet combination therapy of atezolizumab, vemurafenib, and cobimetinib demonstrated improved progression-free survival in patients with BRAF-mutated advanced melanoma. Exploratory biomarker analyses identified potential predictors including tumor mutational burden, interferon-gamma expression, and PD-L1 expression.
ANNALS OF ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Ma del Carmen Alamo, Sebastian Ochenduszko, Guillermo Crespo, Monica Corral, Juana Oramas, Pilar Sancho, Javier Medina, Fernando Garicano, Pedro Lopez, Begona Campos Balea, Analia Rodriguez Garzotto, Eva Munoz-Couselo
Summary: The study evaluated the efficacy of combination therapy with vemurafenib/cobimetinib in terms of durability, finding that one-third of patients achieved a sustained complete response. Factors such as body mass index may influence the durability of the response in patients with advanced melanoma.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Nadine Kretschmer, Christin Durchschein, Antje Hufner, Beate Rinner, Birgit Lohberger, Rudolf Bauer
Summary: In this study, a novel shikonin derivative called SK119 was synthesized and evaluated for its pharmacological effects on human melanoma cells. SK119 exhibited promising activity in a nano-molar range and showed synergistic effects with vemurafenib and cobimetinib, two clinically used melanoma therapeutics. Further research indicates the potential of SK119 in melanoma therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Anna Dawidowska, Paulina Jagodzinska-Mucha, Hanna Kosela-Paterczyk, Sylwia Jaczewska, Pawel Sobczuk, Monika Chelstowska, Maria Kowalska, Honorata Badziak-Sterczewska, Jan Poleszczuk, Piotr Rutkowski, Iwona Lugowska
Summary: This study evaluated the impact of immune-related thyroid adverse events on overall survival rates in patients with melanoma undergoing anti-PD-1 therapy. The results showed that clinically significant hypothyroidism was an independent prognostic factor associated with improved overall survival.
Review
Dermatology
A. Gault, A. E. Anderson, R. Plummer, C. Stewart, A. G. Pratt, N. Rajan
Summary: Checkpoint inhibitors have greatly improved outcomes in metastatic malignant melanoma, but can lead to cutaneous immune-related adverse effects. Anti-CTLA4 therapy has a higher rate of these adverse effects compared to anti-PD1/PDL1 therapies, which are usually managed supportively in mild cases. Delayed presentations of these adverse effects can make them difficult to distinguish from other dermatological conditions, and the identification of predictive biomarkers to manage severe adverse effects remains a challenge.
BRITISH JOURNAL OF DERMATOLOGY
(2021)
Article
Oncology
Carolina A. Ferreira, Pedram Heidari, Bahar Ataeinia, Nicoleta Sinevici, Meghan E. Sise, Robert B. Colvin, Eric Wehrenberg-Klee, Umar Mahmood
Summary: Cancer immunotherapy has greatly improved patient prognosis, but immune-related adverse events remain a challenge. This study demonstrates the use of a granzyme B-targeted PET imaging agent to identify and visualize such events in a murine model, providing potential clinical applications.
CLINICAL CANCER RESEARCH
(2021)
Review
Biochemical Research Methods
Chun Yen Lee, Yi-Ping Phoebe Chen
Summary: Traditional machine learning methods for detecting drug side effects are labor-intensive, while deep learning approaches, with the integration of heterogeneous drug data sources and innovative deployment, can help reduce adverse drug reactions and find replacements for drugs with side effects, as well as diversify drug utilization through drug repurposing.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Chemistry, Multidisciplinary
Shilun Yang, Simeng Li, Junlei Chang
Summary: This study used a virtual screening strategy to identify potential inhibitors of A-FABP in an FDA-approved drug library. Four compounds with the highest scores were identified and further evaluated in cellular assays. Cobimetinib was identified as a novel A-FABP inhibitor with potential for the treatment of metabolic diseases and associated vascular complications.
Article
Biochemistry & Molecular Biology
Elena Elez, Javier Ros, Jose Fernandez, Guillermo Villacampa, Ana Belen Moreno-Cardenas, Carlota Arenillas, Kinga Bernatowicz, Raquel Comas, Shanshan Li, David Philip Kodack, Roberta Fasani, Ariadna Garcia, Javier Gonzalo-Ruiz, Alejandro Piris-Gimenez, Paolo Nuciforo, Grainne Kerr, Rossana Intini, Aldo Montagna, Marco Maria Germani, Giovanni Randon, Ana Vivancos, Ron Smits, Diana Graus, Raquel Perez-Lopez, Chiara Cremolini, Sara Lonardi, Filippo Pietrantonio, Rodrigo Dienstmann, Josep Tabernero, Rodrigo A. Toledo
Summary: In colorectal cancer patients, inactivating mutations in the RNF43 gene are associated with patients' response rates and survival outcomes to anti-BRAF/EGFR therapy. This suggests that the status of the RNF43 gene may serve as a predictive biomarker for patients' clinical outcomes.
Article
Oncology
Katharina C. Kaehler, Ralf Gutzmer, Friedegrund Meier, Lisa Zimmer, Markus Heppt, Anja Gesierich, Kai-Martin Thoms, Jochen Utikal, Jessica C. Hassel, Carmen Loquai, Claudia Pfoehler, Lucie Heinzerling, Martin Kaatz, Daniela Goeppner, Annette Pflugfelder, Ann-Sophie Bohne, Imke Satzger, Lydia Reinhardt, Jan-Malte Placke, Dirk Schadendorf, Selma Ugurel
Summary: The development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment. In the COBIVEM cohort, patients with a mild early exanthema had a superior survival outcome compared to patients with a severe or non early exanthema.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Nicolas Meyer, David Perol, Anne-Benedicte Duval-Modeste, Laila El Adaoui, Yoann Lelarge, Ralph Niarra, Christine Mateus
Summary: This study provides real-world outcomes in France for the vemurafenib-cobimetinib combination available in patients with BRAF-mutant-advanced melanoma. Our data tend to confirm in the real-life setting that this combination therapy is effective in such patients, with a safety profile consistent with previous interventional studies.
Article
Public, Environmental & Occupational Health
Giulio Barteselli, Grant R. Goodman, Yogesh Patel, Ivor Caro, Cloris Xue, Samuel McCallum
Summary: Results from this integrated safety analysis indicate that cobimetinib-associated serous retinopathy can be managed with or without a dose modification of cobimetinib at the discretion of the treating physician. No visual loss or permanent retinal damage was identified on comprehensive ophthalmologic assessments.
Article
Cardiac & Cardiovascular Systems
Weiqi Feng, Qiuji Wang, Chenxi Li, Jinlin Wu, Juntao Kuang, Jue Yang, Ruixin Fan
Summary: This study explores the relationship between admission D-dimer levels and in-hospital major adverse events (MAE) in patients with acute type A aortic dissection (ATAAD). The results indicate that increasing D-dimer levels are independently associated with MAE during hospitalization, suggesting that D-dimer can be used as a useful prognostic biomarker before surgery.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Oncology
Ying Jing, Jingwen Yang, Douglas B. Johnson, Javid J. Moslehi, Leng Han
Summary: Immune-checkpoint inhibitors (ICIs) have been associated with immune-related adverse events (irAEs), a unique spectrum of organ-specific inflammatory toxicities. Recent studies have utilized aggregate clinical data, real-world data, and multi-omics data to investigate the mechanisms and clinical presentations of irAEs. This Perspective provides a summary of the knowledge on irAEs obtained through different sources of "big data".
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Biochemical Research Methods
Zhuohang Yu, Zengrui Wu, Weihua Li, Guixia Liu, Yun Tang
Summary: Identification of adverse drug events (ADEs) is crucial for reducing health risks and improving drug safety assessment. This study introduces a novel network-based method, ADENet, which predicts potential ADEs for drugs within the drug-ADE network as well as novel compounds outside the network. ADENet outperformed previous methods in both model validation and external validation, and showed practical value in predicting ADEs. The method, ADENet, provides a promising tool for ADE prediction and drug safety assessment in drug discovery and development.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Oncology
Sina Vatandoust, Tim Bright, Amitesh Chandra Roy, Muhammad Nazim Abbas, David Ian Watson, Susan Gan, Jeff Bull, Michael Sorich, Alex Scott-Hoy, Lee-Jen Luu, Christos Stelios Karapetis
Summary: This study demonstrated the safety and recommended phase-2 dose of intraperitoneal paclitaxel in combination with cisplatin and capecitabine in an Australian population with gastric cancer and peritoneal involvement. The 12-month survival rate and median survival time were both favorable.
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Ashley M. Hopkins, Ganessan Kichenadasse, Ross A. McKinnon, Ahmad Y. Abuhelwa, Jessica M. Logan, Sarah Badaoui, Christos S. Karapetis, Andrew Rowland, Michael J. Sorich
Summary: The use of PPIs may have a negative impact on the overall survival and progression-free survival of patients receiving atezolizumab plus carboplatin plus paclitaxel or atezolizumab plus BCP treatment for lung cancer, but not for those receiving BCP treatment. This suggests that PPIs may diminish the efficacy of ICIs.
BRITISH JOURNAL OF CANCER
(2022)
Article
Rheumatology
Dala N. Daraghmeh, Ashley M. Hopkins, Catherine King, Ahmad Y. Abuhelwa, Mihir D. Wechalekar, Susanna M. Proudman, Michael J. Sorich, Michael D. Wiese
Summary: This study examined the association between factors influencing female sex hormones and the efficacy of DMARDs in patients with RA. It was found that perimenopausal women were less likely to achieve remission, while the use of exogenous sex hormones was associated with higher remission rates in female RA patients.
Article
Surgery
Mia Shepherdson, Daniel Kilburn, Shahid Ullah, Timothy Price, Christos S. Karapetis, Peter Nguyen, Amanda Townsend, Robert Padbury, Cynthia Piantadosi, Guy Maddern, Scott Carruthers, David Roder, Michael Sorich, Amitesh C. Roy
Summary: A retrospective study of colorectal cancer cases with liver-only metastasis from the South Australian Colorectal Cancer Registry revealed that surgical resection of liver metastasis and primary tumor improved patients' overall survival. Further research is needed on the use of targeted treatments in patients undergoing liver resection.
ANZ JOURNAL OF SURGERY
(2023)
Article
Oncology
Lee X. Li, Federico Cappuzzo, Ignacio Matos, Mark A. Socinski, Ashley M. Hopkins, Michael J. Sorich
Summary: This study evaluated the risk of hyperprogression with the use of immune checkpoint inhibitor (ICI) in the first-, second-, or later-line treatment of advanced non-small cell lung cancer (NSCLC) and provided insights into hyperprogression risk with contemporary first-line ICI treatment.
Article
Oncology
Jessica M. Logan, Ashley M. Hopkins, Carmela Martini, Alexandra Sorvina, Prerna Tewari, Sarita Prabhakaran, Chelsea Huzzell, Ian R. D. Johnson, Shane M. Hickey, Ben S. -Y. Ung, Joanna Lazniewska, Robert D. Brooks, Courtney R. Moore, Maria C. Caruso, Litsa Karageorgos, Cara M. Martin, Sharon O'Toole, Laura Bogue Edgerton, Mark P. Ward, Mark Bates, Stavros Selemidis, Adrian Esterman, Sheena Heffernan, Helen Keegan, Sarah Ni Mhaolcatha, Roisin O'Connor, Victoria Malone, Marguerite Carter, Katie Ryan, Andres Clarke, Nathan Brady, Sonja Klebe, Hemamali Samaratunga, Brett Delahunt, Michael J. Sorich, Kim Moretti, Lisa M. Butler, John J. O'Leary, Douglas A. Brooks
Summary: A novel biomarker panel (Appl1, Sortilin and Syndecan-1) was found to be a strong independent predictor for both clinical and biochemical recurrence outcomes, with higher prediction performance than traditional grading. The study also found that biomarker-assisted assessment had better predictive performance for evaluating the risk of biochemical recurrence and clinical recurrence in patients with prostate cancer.
Article
Biochemistry & Molecular Biology
Arkady T. Manning-Bennett, Julie Cervesi, Pierre-Alain Bandinelli, Michael J. Sorich, Ashley M. Hopkins
Summary: The use of antibiotics within a +/- 6-week window is significantly associated with worse progression-free survival (PFS) and overall survival (OS) outcomes in advanced NSCLC patients treated with or without atezolizumab. The impact of antibiotics on ICIs efficacy may be related to changes in the microbiome.
Editorial Material
Oncology
Ashley M. Hopkins, Jessica M. Logan, Ganessan Kichenadasse, Michael J. Sorich
Summary: On November 30, 2022, OpenAI released ChatGPT, an advanced AI with the capability to write, solve coding problems, and answer questions. This communication highlights the potential of ChatGPT and similar AI assistants in becoming vital virtual aids for patients and healthcare providers. The evaluation showed ChatGPT's impressive ability to generate interpretable responses, reducing the likelihood of causing alarm unlike the feature snippet of Google. This commentary emphasizes the necessity for regulators and healthcare professionals to establish quality standards and raise patient awareness regarding the current limitations of emerging AI assistants.
JNCI CANCER SPECTRUM
(2023)
Article
Medicine, General & Internal
Natansh D. Modi, Ganessan Kichenadasse, Tammy C. Hoffmann, Mark Haseloff, Jessica M. Logan, Areti A. Veroniki, Rebecca L. Venchiarutti, Amelia K. Smit, Haitham Tuffaha, Harindra Jayasekara, Arkady Manning-Bennet, Erin Morton, Ross A. Mckinnon, Andrew Rowland, Michael J. Sorich, Ashley M. Hopkins
Summary: This article presents policy and process updates to the PhRMA/EFPIA 2013 data sharing commitments, aiming to enhance the sharing and accessibility of participant-level data, clinical study reports, protocols, statistical analysis plans, lay summaries, and result publications from pharmaceutical industry-sponsored trials. The proposed improvements aim to develop a data sharing ecosystem that supports science and patient-centered care. Despite challenges, enhancing data sharing is necessary for efficient resource utilization, increased scientific collaboration, and better decision-making for patients and healthcare professionals.
Article
Oncology
Adel Shahnam, Udit Nindra, Jayesh Desai, Rina Hui, Marc Buyse, Ashley M. Hopkins, Michael J. Sorich
Summary: This study evaluated the relationship between progression-free survival (PFS), time to deterioration in quality of life (QOL) or physical function, and overall survival in clinical trials of solid malignancies. The results showed that time to deterioration in physical function had a higher association with overall survival, particularly for immune checkpoint inhibitor treatment. Combining PFS and time to deterioration in physical function may provide better prediction of overall survival benefit in clinical trials of immune checkpoint inhibitors.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Meeting Abstract
Oncology
Natansh Modi, Ahmad Y. Abuhelwa, Andrew Rowland, Bradley D. Menz, Ross Allan McKinnon, Michael J. Sorich, Ashley Mark Hopkins
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemical Research Methods
Zivile Useckaite, Lauren A. Newman, Ashley M. Hopkins, Sonja Klebe, Alex D. Colella, Nusha Chegeni, Ruth Williams, Michael J. Sorich, A. David Rodrigues, Tim K. Chataway, Andrew Rowland
Summary: The study aimed to compare the proteomic profiles of extracellular vesicles (EVs) isolated from liver tissue and the extracellular space. The results showed the potential of liver-derived EVs as a liquid biopsy for understanding the functional status of the liver.
