Article
Gastroenterology & Hepatology
Franck Carbonnel, Emilie Routier, Thierry Lazure, Charlotte Mussini, Christophe Bellanger, Carine Merklen, Bakhtiar Bejou, Anthony Buisson, Aurelien Amiot, Antoine Meyer, Catherine Dong, Caroline Robert
Summary: This study provides the first systematic description of colitis caused by dual blockade of BRAF and MEK kinases in the treatment of melanoma. The study found that severe colitis characterized by ulcerations of the right colon can occur, leading to symptoms such as diarrhea, rectal bleeding, abdominal pain, and intestinal obstruction. In some cases, the colitis was associated with ischemic changes and inflammation.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Katrin Pape, Maria Protopapa, Muriel Schraad, Falk Steffen, Frauke Zipp, Stefan Bittner
Summary: Treatment of malignant melanoma with BRAF/MEK inhibitors may exacerbate pre-existing multiple sclerosis (MS) disease.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Hima Patel, Rosalin Mishra, Nour Yacoub, Samar Alanazi, Mary Kate Kilroy, Joan T. Garrett
Summary: Melanoma, accounting for only 4% of skin cancer, is a major cause of skin cancer related deaths. Resistance to FDA approved drugs dabrafenib and trametinib in treating BRAFV600E melanoma is mediated by the activation of IGF1R and IR. Combining dabrafenib and trametinib with IGF1R/IR inhibitor BMS-754807 effectively inhibits proliferation and tumor growth, offering potential treatment options for patients with BRAF-mutant melanoma.
Article
Biochemistry & Molecular Biology
Emmanuelle M. Ruiz, Solomon A. Alhassan, Youssef Errami, Zakaria Y. Abd Elmageed, Jennifer S. Fang, Guangdi Wang, Margaret A. Brooks, Joe A. Abi-Rached, Emad Kandil, Mourad Zerfaoui
Summary: A 13-gene panel was identified to accurately predict resistance to BRAF/MEK inhibitor therapy in melanoma patients. Dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a treatment-resistant landscape, and HMOX1-mediated mitochondrial stress response was identified as a potential key driver of resistance. These findings highlight the importance of these genes in predicting treatment outcomes and targeting underlying mechanisms to reduce resistance development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Avirup Guha, Prantesh Jain, Michael G. Fradley, Daniel Lenihan, Jahir M. Gutierrez, Chhavi Jain, Marcos de Lima, Jill S. Barnholtz-Sloan, Guilherme H. Oliveira, Afshin Dowlati, Sadeer Al-Kindi
Summary: In comparison to monotherapy with BRAF inhibitors, combination therapy with BRAF/MEK inhibitors is associated with increased cardiovascular adverse events (CVAEs), primarily heart failure (HF) and hypertension, as confirmed in two independent real-world cohorts.
Article
Oncology
Morgan Homan, Govind Warrier, Christopher D. Lao, Sarah Yentz, Shawna Kraft, Leslie A. Fecher
Summary: This study describes the treatment-related toxicities of adjuvant dabrafenib and trametinib combination therapy for patients with resected melanoma and finds that the majority of patients experience treatment-limiting toxicities. Therefore, close monitoring of patients is necessary during treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Charles-Edouard Decorads, Aurelien Lambert, Veronique Roch, Laetitia Imbert, Mathieu Perrin, Marine Claudin, Julia Salleron, Nicolas Veran, Zohra Lamiral, Catherine Henneton, Pierre-Yves Marie
Summary: This study evaluates the use of ultra-low-dose ERNA for first-line LVEF monitoring in breast cancer women treated with potentially cardiotoxic drugs and analyzes patient outcome based on the ERNA results. The results show that ultra-low-dose ERNA provides consistent detection of breast cancer therapy-related cardiotoxicity and confirms excellent cardiac outcome for the majority of women.
JOURNAL OF NUCLEAR CARDIOLOGY
(2023)
Review
Oncology
Neha Makunda, Srilakshmi Vallabhaneni, Benedicte Lefebvre, Michael G. Fradley
Summary: Melanoma, the least common but most dangerous skin cancer, has seen significant improvement in prognosis with the emergence of targeted and immunotherapies. However, these treatments can lead to treatment-limiting side effects, particularly cardiovascular toxicities. Thus, a multidisciplinary approach is crucial to ensure patients receive effective melanoma treatments while minimizing adverse cardiovascular effects.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2022)
Article
Dermatology
Dimitrios C. Ziogas, Frosso Konstantinou, Spyros Bouros, Maria Theochari, Helen Gogas
Summary: The management and prognosis of BRAF-mutant metastatic melanoma have undergone significant changes with the introduction of immune checkpoint inhibitors and molecularly targeted agents. Combining BRAF/MEK inhibitors with immune checkpoint inhibitors is thought to improve sensitivity to immunotherapy, with ongoing clinical trials exploring optimal timing and eligible patient subsets for these regimens.
AMERICAN JOURNAL OF CLINICAL DERMATOLOGY
(2021)
Article
Oncology
Martin Salzmann, Alexander Wald, Henner Stege, Carmen Loquai, Lisa Zimmer, Kinan M. Hayani, Lucie Heinzerling, Ralf Gutzmer, Alexander H. Enk, Jessica C. Hassel
Summary: Patients with metastasized melanoma can be treated with different combinations of targeted therapy tablets. A study conducted at six German cancer centers found that switching to a different combination can be a feasible and rational approach when the initial combination is not tolerated well. The new combination was overall better tolerated and had similar efficacy, but new side effects may occur.
Article
Oncology
Anna Stagno, Sabrina Vari, Alessio Annovazzi, Vincenzo Anelli, Michelangelo Russillo, Francesco Cognetti, Virginia Ferraresi
Summary: This article reports the experience of rechallenging with BRAF and MEK inhibitors in patients with metastatic BRAF-mutated melanoma after progression with kinase inhibitors and immunotherapy. Two out of four patients had partial response, one patient had rapid disease progression, and another patient showed clinical benefit and stable disease. Adverse events were manageable and better tolerated at rechallenge by two patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Pui-Kei Wu, Seung-Keun Hong, Jong-In Park
Summary: The study found that RNA interference of mortalin can induce cell death in vemurafenib-resistant B-Raf mutant melanoma cells, and chemical inhibition of MEK1/2 and ERK1/2 can suppress mortalin depletion-induced death. Therefore, mortalin may serve as a potential therapeutic target for BRAFi-resistant BRAF mutant tumors.
Article
Oncology
Lukas Peiffer, Farnoush Farahpour, Ashwin Sriram, Ivelina Spassova, Daniel Hoffmann, Linda Kubat, Patrizia Stoitzner, Thilo Gambichler, Antje Sucker, Selma Ugurel, Dirk Schadendorf, Jurgen C. Becker
Summary: The study found that treatment with BRAF/MEK inhibitors in melanoma patients allows for an increased expansion of pre-existing melanoma-specific T cells by inducing T-bet and TCF7.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Zeynep Eroglu, Y. Ann Chen, Inna Smalley, Jiannong Li, Joseph K. Markowitz, Andrew S. Brohl, Leticia Tetteh, Hayley Taylor, Vernon K. Sondak, Nikhil I. Khushalani, Keiran S. M. Smalley
Summary: In this study, the efficacy and safety of vemurafenib and cobimetinib in combination with different doses of the HSP90 inhibitor XL888 for the treatment of advanced melanoma were explored. The study found that this combination therapy showed activity in some patients, but also had significant toxicity.
Article
Oncology
Youjia Tian, Jiang Zhou, Xinxin Chai, Zejun Ping, Yurong Zhao, Xin Xu, Chi Luo, Jinghao Sheng
Summary: In this study, the researchers found that TCF12 plays an oncogenic role in melanoma progression. They observed that TCF12 expression increases as melanoma progresses, and high expression is associated with poor survival outcomes in melanoma patients. Functionally, TCF12 enhances melanoma proliferation and metastasis, as well as sensitivity to BRAF(V600E)-targeted therapy. The researchers also identified TGFB2 as a direct downstream target of TCF12, mediating its pro-tumorigenic effects.
Article
Oncology
Eva Ellebaek, Aimilia Schina, Henrik Schmidt, Charlotte Aaquist Haslund, Lars Bastholt, Inge Marie Svane, Marco Donia
Summary: This study found that initiation of immunotherapy in summer is associated with prolonged survival in patients with BRAF wild-type melanoma in Denmark.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Oncology
Sidsel Pedersen, Rikke B. B. Holmstroem, Annika von Heymann, Laerke K. K. Tolstrup, Kasper Madsen, Morten Aagaard Petersen, Charlotte A. A. Haslund, Christina H. H. Ruhlmann, Henrik Schmidt, Christoffer Johansen, Inge Marie Svane, Eva Ellebaek
Summary: This study investigates the impact of adjuvant immunotherapy on health-related quality of life (HRQoL) in patients with resected melanoma. The findings suggest that HRQoL is lowest in patients who ended therapy 0-6 months ago and that fatigue is more severe in this group. Patients in active treatment for >6 months also have lower HRQoL and more fatigue compared to those who started treatment 0-6 months ago. However, patients who ended therapy >6 months ago have higher HRQoL and less fatigue. HRQoL is associated with treatment status, comorbidity, civil status, and employment status.
Editorial Material
Gastroenterology & Hepatology
Emilie K. Dahl, Osama K. Abed, Jens Kjeldsen, Marco Donia, Inge M. Svane, Anders Dige, Jorgen S. Agnholt, Jacob T. Bjerrum, Jakob B. Seidelin
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemical Research Methods
Anders H. Kverneland, Ole Ostergaard, Kristina Bennet Emdal, Inge Marie Svane, Jesper Velgaard Olsen
Summary: This study demonstrates that enrichment of extracellular vesicles (EVs) by ultracentrifugation can significantly increase the depth of the plasma proteome analysis. By optimizing the workflow, over two thousand proteins can be quantified in a short time using label-free quantification and data independent acquisition (DIA), enabling high-throughput analysis of plasma samples and supporting potential biomarker discovery in the future.
Article
Medicine, General & Internal
Nicklas Juel Spindler, Gitte Fredberg Persson, Susann Theile, Dorte Lisbeth Nielsen, Estrid Hogdall, Gina Al-Farra, Helle Westergren Hendel, Torben Lorentzen, Inge Marie Svane, Henriette Lindberg, Rikke Lovendahl Eefsen
Summary: This study aims to investigate the efficacy of combining SBRT and CPI treatment in patients with mCRPC. A total of 80 evaluable patients who have progressed after multiple lines of treatment will be enrolled and receive ipilimumab and nivolumab combination therapy, with some patients also receiving SBRT. The primary endpoints are objective response rate and PSA response rate, and secondary endpoints include safety, radiographic progression-free survival, clinical benefit rate, duration of response, PSA-progression-free survival beyond 12 weeks, quality of life, and overall survival. The results will be published in an international peer-reviewed journal.
Article
Oncology
Amalie Valentin, Anne Kirstine Hundahl Moller, Jesper Andreas Palshof, Bo Broberg, Eva Gravesen, Inge Marie Svane, Ditte Hansen
Summary: This study aimed to describe the incidence and causes of AKI in patients treated with immune checkpoint inhibitors. The study showed that 16% of malignant melanoma patients and 25% of metastatic renal cell carcinoma patients developed AKI. Some of these cases may be related to immune checkpoint inhibitors or the use of proton pump inhibitors.
Letter
Gastroenterology & Hepatology
Emilie Dahl, Osama Abed, Jorgen Agnholt, Jacob Bjerrum, Anders Dige, Jens Kjeldsen, Inge Svane, Marco Donia, Jakob Seidelin
Summary: This article is linked to Dahl et al papers. To view these articles, visit...
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Neel Maria Helvind, Marie Brinch-Moller Weitemeyer, Annette Hougaard Chakera, Helle Westergren Hendel, Eva Ellebaek, Inge Marie Svane, Mette Wanscher Kjaerskov, Sophie Bojesen, Helle Skyum, Soren Kjaer Petersen, Lars Bastholt, Christoffer Johansen, Pernille Envold Bidstrup, Lisbet Rosenkrantz Holmich
Summary: This study aimed to determine the impact of surveillance with routine FDG PET-CT on hazard, cumulative incidence, and absolute risk of overall, locoregional, and distant recurrence detection in patients with stage IIB to IIID cutaneous melanoma. The study found that patients with stage IIB to IIID melanoma followed with routine FDG PET-CT had a 51% increased hazard of distant recurrence detection within the first two years of surveillance.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Review
Oncology
Tine J. Monberg, Troels H. Borch, Inge M. Svane, Marco Donia
Summary: Treatment with tumor-infiltrating lymphocytes (TIL) has been proven to be safe, feasible, and effective for patients with metastatic melanoma. However, its implementation on a larger scale is currently limited due to the lack of regulatory approvals. This review discusses the current knowledge of TIL therapy and addresses the practical, logistic, and economic challenges associated with its widespread implementation.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Arianna Draghi, Mario Presti, Agnete W. P. Jensen, Christopher A. Chamberlain, Benedetta Albieri, Anne-Christine K. Rasmussen, Mads H. Andersen, Michael D. Crowther, Inge Marie Svane, Marco Donia
Summary: Our study demonstrates that exploiting tumor-specific cytotoxic CD4(+) TILs could help overcome resistance to ICB mediated by IFN gamma-signaling loss in MHCIIconst(+) melanomas.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Rasmus Erik Johansson Mortensen, Morten Orebo Holmstrom, Thomas Landkildehus Lisle, Jane P. Hasselby, Gro L. Willemoe, Ozcan Met, Inge Marie Svane, Julia Johansen, Dorte L. Nielsen, Inna M. Chen, Mads Hald Andersen
Summary: This study investigated the significance of TGF-beta-specific T-cell immunity in patients with pancreatic cancer treated with ICI combined with radiotherapy. The results showed that patients with a strong TGF-beta-specific immune response had longer progression-free and overall survival compared to those with a weak or no response. It was also found that TGF-beta-specific T cells could recognize and enhance immune responses. Thus, combining TGF-beta vaccination with ICI/radiotherapy may benefit patients with pancreatic cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Cathrine Lund Lorentzen, Julie Westerlin Kjeldsen, Eva Ehrnrooth, Mads Hald Andersen, Inge Marie Svane
Summary: Summary: This study presented the long-term follow-up results of the IDO/PD-L1 vaccine and nivolumab combination therapy in cohort A, showing promising efficacy with high overall response rates and durable responses. However, cohort B did not show significant clinical effects.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Anne Vest Soerensen, Jakob Kjellberg, Rikke Ibsen, Lars Bastholt, Henrik Schmidt, Inge Marie Svane
Summary: This study aimed to investigate the health care costs and loss of productivity after implementing new agents for metastatic melanoma. The results showed that the implementation of targeted therapy and checkpoint inhibitors increased medicine costs more than three-fold for long-term survivors. However, total health care costs excluding medicine costs were lower for long-term survivors in 2012-2016 compared to 2007-2011. Importantly, productivity increased for long-term survivors in 2012-2016.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Aimilia Schina, Sidsel Pedersen, Anne -Louise Spenning, Olivia Kaas Laursen, Cecilia Pedersen, Charlotte Aaquist Haslund, Henrik Schmidt, Lars Bastholt, Inge Marie Svane, Eva Ellebaek, Marco Donia
Summary: This study analyzed the real-world impact of modern treatments on the long-term survival of patients with metastatic melanoma. The introduction of therapies such as anti-PD-1 led to sustained improved survival in patients, regardless of their eligibility for clinical trials. A prognostic model was developed to predict the survival of newly diagnosed patients, providing a useful tool for improving patient information.
EUROPEAN JOURNAL OF CANCER
(2023)