Article
Oncology
Annabel H. S. Alig, Volker Heinemann, Michael Geissler, Ludwig Fischer von Weikersthal, Thomas Decker, Kathrin Heinrich, Swantje Held, Lena Weiss, Ludwig Fischer E. von Weikerstha, Nicolas Moosmann, Arndt Stahler, Ivan Jelas, Annika Kurreck, Jobst C. von Einem, Anke C. Reinacher-Schick, Andrea Tannapfel, Clemens Giessen-Jung, Sebastian Stintzing, Dominik P. Modest
Summary: The exact primary tumor location in RAS/BRAF wild-type mCRC has a predictive impact on disease spread and overall survival, as well as potential impact on anti-EGFR agent efficacy. Further studies are necessary to confirm and investigate these results.
Article
Gastroenterology & Hepatology
Hong-Min Ahn, Duck-Woo Kim, Hyeon Jeong Oh, Hyung Kyung Kim, Hye Seung Lee, Tae Gyun Lee, Hye-Rim Shin, In Jun Yang, Jeehye Lee, Jung Wook Suh, Heung-Kwon Oh, Sung-Bum Kang
Summary: This study retrospectively evaluated the clinicopathological characteristics and prognostic value of codon-specific KRAS mutations, especially in codon 13. The study provides evidence that KRAS codon 13 mutation is less likely to serve as a prognostic biomarker than codon 12 mutation for colorectal cancer in a large-scale cohort.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Biology
Michael Gerber, Sanjay Goel, Radhashree Maitra
Summary: This study analyzed the GTP binding dynamics of mutant KRAS protein and found that the mutant type has lower affinity for GTP compared to wildtype KRAS. Additionally, conformational changes and other subtle structural differences were observed in the mutant KRAS protein.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Pathology
Seung-Hee Cho, Byung-Joon Seung, Soo-Hyeon Kim, Min-Kyung Bae, Ha-Young Lim, Jung-Hyang Sur
Summary: This study evaluated EGFR expression levels in canine intestinal adenocarcinomas, finding that they were higher than in non-neoplastic tissue at both protein and mRNA levels. Additionally, wild-type sequences were observed in the EGFR, KRAS, and BRAF genes in all 13 samples, aiding in the development of anti-EGFR agents for canine intestinal adenocarcinoma.
VETERINARY PATHOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Meiqin Yuan, Zeng Wang, Wangxia Lv, Hongming Pan
Summary: Currently, the combination of anti-EGFR mAb and chemotherapy is the first-line treatment standard for RAS wild-type mCRC. However, there is ongoing debate regarding the use of anti-EGFR mAb for maintenance treatment after the initial treatment. Despite the lack of evidence from large-scale clinical trials, more studies support the use of anti-EGFR mAb for maintenance therapy, although cost and drug resistance remain concerns.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Pharmacology & Pharmacy
Reyhaneh Moradi-marjaneh, Fereshteh Asgharzadeh, Elnaz Khordad, Mahdi Moradi Marjaneh
Summary: The prognostic value of cfDNA in mCRC patients treated with EGFR inhibitors, particularly in identifying KRAS and BRAF mutations, is highlighted. Assessing mutational status in circulating cell free DNA may offer advantages in patient selection by potentially better representing the dynamicity of tumor genetic status compared to tumor tissue.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Oncology
Martin S. Schulz, Sebastian Wolf, Vera Struck, Niklas Thomas, Gabriele Husman, Stefan Zeuzem, Christine Koch, Joerg Trojan, Andreas Anton Schnitzbauer, Wolf Otto Bechstein, Oliver Waidmann
Summary: This real-world study from a large oncology center in Germany provides evidence that anti-EGFR re-exposure may benefit patients with advanced CRC, regardless of the reason for prior discontinuation.
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
Emilie Hafliger, Alessandra Boccaccino, Alexandra Lapeyre-Prost, Audrey Perret, Claire Gallois, Maria Antista, Lorenzo Pilla, Thierry Lecomte, Mario Scartozzi, Emilie Soularue, Lisa Salvatore, Vincent Bourgeois, Massimiliano Salati, David Tougeron, Ludovic Evesque, Jean-Nicolas Vaillant, Reem El-Khoury, Sara Lonardi, Chiara Cremolini, Julien Taieb
Summary: The combination of anti-BRAF and anti-EGFRs shows efficacy in patients with BRAFm mCRC previously treated with an anti-EGFR agent. The results of this retrospective study suggest that this combination could be a valuable treatment option for patients with limited therapeutic alternatives.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Dentistry, Oral Surgery & Medicine
Tamara da Silva Vieira, Leticia Martins Guimaraes, Marina Goncalves Diniz, Bianca Gomes-Fernandes, Wilma Terezinha Anselmo-Lima, Edwin Tamashiro, Luciana Bastos-Rodrigues, Luiz De Marco, Ricardo Santiago Gomez, Fabiana Cardoso Pereira Valera, Carolina Cavalieri Gomes
Summary: This study suggests that pathogenic mutations in KRAS, BRAF, and EGFR genes are not frequent events in CRSwNP, and if they occur, they might represent marginal events at best.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Frank Aboubakar Nana, Sebahat Ocak
Summary: Osimertinib is now a standard first-line treatment for NSCLC with specific EGFR mutations, however, resistance mechanisms are inevitable. This study discusses acquired resistance mechanisms, specifically the BRAF V600 mutation, in EGFR-mutant NSCLC patients treated with Osimertinib in combination with dabrafenib and trametinib.
Article
Oncology
Iris van 't Erve, Nina J. Wesdorp, Jamie E. Medina, Leonardo Ferreira, Alessandro Leal, Joost Huiskens, Karen Bolhuis, Jan-Hein T. M. van Waesberghe, Rutger-Jan Swijnenburg, Daan van den Broek, Victor E. Velculescu, Geert Kazemier, Cornelis J. A. Punt, Gerrit A. Meijer, Remond J. A. Fijneman
Summary: Patients with mCRC carrying a KRAS A146 mutation have higher tumor burden and worse clinical outcomes, and may benefit from more intensive treatments.
JCO PRECISION ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Javier Vaquero, Allan Pavy, Ester Gonzalez-Sanchez, Mark Meredith, Ander Arbelaiz, Laura Fouassier
Summary: EGFR can be targeted through selective tyrosine kinase inhibitors and monoclonal antibodies, but the majority of patients do not benefit due to the presence of drug resistance mechanisms. Extensive research is being conducted to find novel approaches to overcome resistance.
DRUG RESISTANCE UPDATES
(2022)
Article
Chemistry, Medicinal
Samar A. El-Kalyoubi, Hesham A. M. Gomaa, Elshimaa M. N. Abdelhafez, Mohamed Ramadan, Fatimah Agili, Bahaa G. M. Youssif
Summary: The investigation focused on designing and synthesizing purine/pteridine-based derivatives as dual inhibitors of EGFR and BRAF(V600E) for targeted cancer treatment. The majority of the compounds displayed promising antiproliferative activity on cancer cell lines. Compounds 5a, 5e, and 7e of purine-based and pteridine-based scaffolds were identified as the most potent hits, exhibiting strong anti-proliferative and EGFR inhibitory activities. However, the results suggested that BRAF(V600E) may not be a viable target for this class of organic compounds. Molecular docking studies provided insight into possible binding modes at the active sites of EGFR and BRAF(V600E).
Article
Multidisciplinary Sciences
Yoojoo Lim, Sheehyun Kim, Jun-Kyu Kang, Hwang-Phill Kim, Hoon Jang, Hyojun Han, Hyoki Kim, Min Jung Kim, Kyung-Hun Lee, Seung-Bum Ryoo, Ji Won Park, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim
Summary: A study on ctDNA analysis in mCRC patients revealed that specific gene mutations are closely associated with disease progression and treatment outcomes. Particularly, changes in VAF can serve as predictive indicators for early treatment response and disease progression.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Gastroenterology & Hepatology
Sarah Klauss, Mark Op den Winkel, Jorg Schirra, Markus Rentsch, Julia Mayerle, Jens H. L. Neumann, Enrico N. De Toni
Article
Oncology
Greta Sommerhauser, Annika Kurreck, Alexander Beck, Uli Fehrenbach, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Lothar Mueller, Alexander O. Koenig, Ludwig F. v. Weikersthal, Eray Goekkurt, Siegfried Haas, Arndt Stahler, Volker Heinemann, Swantje Held, Annabel H. S. Alig, Stefan Kasper, Sebastian Stintzing, Tanja Trarbach, Dominik P. Modest
Summary: Depth of response (DpR) is an important end-point in clinical trials for patients with RAS wild-type metastatic colorectal cancer. This study investigated the overall DpR and its impact on prognosis and prediction in patients receiving induction therapy followed by maintenance therapy. The results showed that DpR to induction therapy was prognostic but not predictive for the efficacy of consecutive maintenance therapy.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
M. Buettelmann, R. D. Hofheinz, A. Kroecher, U. Ubbelohde, S. Stintzing, A. Reinacher-Schick, M. Bornhaeuser, G. Folprecht
Summary: Geriatric assessment (GA) has limited influence on treatment recommendations for elderly cancer patients, highlighting the need for further research and education in this area.
Article
Oncology
Klara Dorman, Danmei Zhang, Wolfgang G. Kunz, Martin Angele, Jens Neumann, Alexander Burges, Michael Von Bergwelt-Baildon, Volker Heinemann, Stefan Boeck, Clemens Giessen-Jung
Summary: This article reports a rare case of a 55-year-old woman with previously undiagnosed endometriosis presenting with mediastinal cancer of unknown primary (CUP) and synchronous rectal adenocarcinoma. It emphasizes the importance of diagnosing and treating multiple malignancies at large interdisciplinary centers.
ANTICANCER RESEARCH
(2023)
Review
Oncology
Erika Martinelli, Dirk Arnold, Andres Cervantes, Sebastian Stintzing, Eric Van Cutsem, Josep Tabernero, Julien Taieb, Harpreet Wasan, Fortunato Ciardiello
Summary: This article reviews the current knowledge and consensus management on the clinical management of BRAFV600E-mutant metastatic colorectal cancer (mCRC). The treatment landscape for this specific type of mCRC has changed greatly due to the emergence of molecular targeted therapies and immune checkpoint inhibitors. Tumor tissue analysis for DNA mismatch repair/microsatellite status and KRAS, NRAS, and BRAF mutational status is mandatory for appropriate clinical management and treatment decisions.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Alessandra Raimondi, Federico Nichetti, Arndt Stahler, Harpreet S. Wasan, Enrique Aranda, Giovanni Randon, Annika Kurreck, Angela M. Meade, Eduardo Diaz-Rubio, Monica Niger, Sebastian Stintzing, Federica Palermo, Tanja Trarbach, Michele Prisciandaro, Greta Sommerhauser, David Fisher, Federica Morano, Filippo Pietrantonio, Dominik P. Modest
Summary: This study analyzed the data from four randomized phase II trials and supported the use of 5-FU/LV plus anti-EGFR as the preferred maintenance regimen. The results also suggested an individualized approach to maintenance treatment based on tumor and patient characteristics.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Martin J. Raftery, Alexander Sebastian Franzen, Clarissa Radecke, Abdelhadi Boulifa, Guenther Schoenrich, Sebastian Stintzing, Jens-Uwe Blohmer, Gabriele Pecher
Summary: There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models and were resistant to immunosuppression by the tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Sebastian Stintzing, Kathrin Heinrich, David Tougeron, Dominik Paul Modest, Ingo Schwaner, Jan Eucker, Rudolf Pihusch, Martina Stauch, Florian Kaiser, Christoph Kahl, Meinolf Karthaus, Christian Mueller, Christof Burkart, Anke Reinacher-Schick, Stefan Kasper-Virchow, Ludwig Fischer von Weikersthal, Beate Krammer-Steiner, Gerald Wolfgang Prager, Julien Taieb, Volker Heinemann
Summary: This clinical trial investigated the efficacy of triplet chemotherapy combined with either cetuximab or bevacizumab in previously untreated BRAF(V600E)-mutant metastatic colorectal cancer (mCRC) patients. The results showed that bevacizumab-based chemotherapy remains the preferable first-line treatment for patients with BRAF(V600E)-mutant mCRC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Arndt Stahler, Beeke Hoppe, Il-Kang Na, Luisa Keilholz, Lothar Mueller, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Ludwig Fischer von Weikersthal, Eray Goekkurt, Stefan Kasper, Andreas Jay Kind, Annika Kurreck, Annabel Helga Sophie Alig, Swantje Held, Anke Reinacher-Schick, Volker Heinemann, David Horst, Armin Jarosch, Sebastian Stintzing, Tanja Trarbach, Dominik Paul Modest
Summary: In patients with RAS wild-type mCRC, CMSs were evaluated as prognostic and predictive biomarkers. The addition of Pmab to FU/FA maintenance therapy was associated with longer PFS and OS in CMS2/4 tumors, whereas no benefit was observed in CMS1/3 tumors.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Medicine, General & Internal
Christopher C. M. Neumann, Francois Schneider, Georg Hilfenhaus, Loredana Vecchione, Christian Benzing, Jana Ihlow, Uli Fehrenbach, Thomas Malinka, Ulrich Keilholz, Sebastian Stintzing, Uwe Pelzer
Summary: In addition to being risk factors for pancreatic cancer, parameters such as smoking, diabetes, or obesity might also act as potential prognostic factors for the survival of patients initially diagnosed with pancreatic cancer. By implementing one of the largest retrospective study cohorts, potential prognostic factors for survival were evaluated and various metabolic markers were identified.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Christopher C. M. Neumann, Francois Schneider, Georg Hilfenhaus, Loredana Vecchione, Matthaeus Felsenstein, Jana Ihlow, Dominik Geisel, Steffen Sander, Johann Pratschke, Sebastian Stintzing, Ulrich Keilholz, Uwe Pelzer
Summary: Inflammation markers, including NRL, PLR, LMR, CAR, and the new combined score IBI, have been identified as independent prognostic markers for overall survival in pancreatic cancer patients. These findings highlight the importance of inflammation in pancreatic cancer, provide easily accessible prognostic values, and may aid in patient stratification for trials targeting inflammation or immune response.
Article
Oncology
Till de Bortoli, Manuela Benary, Peter Horak, Mario Lamping, Sebastian Stintzing, Ingeborg Tinhofer, Serge Leyvraz, Reinhold Schaefer, Frederick Klauschen, Ulrich Keller, Albrecht Stenzinger, Stefan Froehling, Razelle Kurzrock, Ulrich Keilholz, Damian T. Rieke, Ivan Jelas
Summary: In this study, it was found that high tumour mutational burden (TMB) was associated with unfavorable outcome in patients receiving molecularly matched therapy. Patients with high TMB had significantly shorter overall survival and progression-free survival compared to those with low TMB. Additionally, a significant correlation was observed between co-occurring driver mutations and TMB.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Alexej Ballhausen, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Lothar Mueller, Alexander Otto Koenig, Ludwig Fischer von Weikersthal, Greta Sommerhaeuser, Annabel Helga Sophie Alig, Eray Goekkurt, Johanna Wanda Meyer-Knees, Annika Kurreck, Arndt Stahler, Swantje Held, Stefan Kasper, Kathrin Heinrich, Volker Heinemann, Sebastian Stintzing, Tanja Trarbach, Dominik Paul Modest
Summary: The addition of Panitumumab to fluorouracil and folinic acid maintenance therapy in patients with RAS wild-type metastatic colorectal cancer prolongs progression-free survival without negative impact on health-related quality of life.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Alexander J. Ohnmacht, Arndt Stahler, Sebastian Stintzing, Dominik P. Modest, Julian W. Holch, C. Benedikt Westphalen, Linus Hoelzel, Marisa K. Schuebel, Ana Galhoz, Ali Farnoud, Minhaz Ud-Dean, Ursula Vehling-Kaiser, Thomas Decker, Markus Moehler, Matthias Heinig, Volker Heinemann, Michael P. Menden
Summary: Precision medicine has revolutionized cancer treatments, but actionable biomarkers are still rare. In this study, the authors develop a framework called OncoBird to analyze the molecular and biomarker landscape of randomized controlled clinical trials, and apply it to a phase III trial investigating metastatic colorectal carcinoma patients.
NATURE COMMUNICATIONS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Felix O. Hofmann, Volker Heinemann, Melvin D'Anastasi, Alena B. Gesenhues, Nina Hesse, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Markus Moehler, Florian Kaiser, Tobias Heintges, Christoph Kahl, Frank Kullmann, Werner Scheithauer, Hartmut Link, Dominik P. Modest, Sebastian Stintzing, Julian W. Holch
Summary: This study aimed to improve the predictive accuracy of early tumor shrinkage (ETS) by using semi-automated volumetry instead of standard diametric measurements. The results showed that continuous diametric and volumetric ETS similarly predicted survival, and a threshold of 45% for volumetric ETS and 20% for diametric ETS accurately identified short-term survivors.
EUROPEAN RADIOLOGY
(2023)
