Article
Medicine, General & Internal
Priscilla K. Brastianos, Erin Twohy, Susan Geyer, Elizabeth R. Gerstner, Timothy J. Kaufmann, Shervin Tabrizi, Brian Kabat, Julia Thierauf, Michael W. Ruff, Daniela A. Bota, David A. Reardon, Adam L. Cohen, Macarena I. De La Fuente, Glenn J. Lesser, Jian Campian, Pankaj K. Agarwalla, Priya Kumthekar, Bhupinder Mann, Shivangi Vora, Michael Knopp, A. John Iafrate, William T. Curry, Daniel P. Cahill, Helen A. Shih, Paul D. Brown, Sandro Santagata, Fred G. Barker, Evanthia Galanis
Summary: This study investigated the safety and efficacy of the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in patients with papillary craniopharyngiomas. Results showed that 15 out of 16 patients had a durable objective partial response or better to the therapy. The median reduction in tumor volume was 91%, and the progression-free survival rates at 12 and 24 months were 87% and 58% respectively.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Yutuan Wu, Jie Huang, Cristina Ivan, Yunjie Sun, Shaolin Ma, Lingegowda S. Mangala, Bryan M. Fellman, Diana L. Urbauer, Nicholas B. Jennings, Prahlad Ram, Robert L. Coleman, Wei Hu, Anil K. Sood
Summary: The study revealed that the MAPK pathway is activated in dasatinib-resistant uterine cancer cells, and EphrinA1-mediated MEK inhibition can overcome resistance. Dual targeting of EphA2 and MEK, along with chemotherapy, should be considered for future clinical development.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Oncology
Alexey V. Sorokin, Preeti Kanikarla Marie, Lea Bitner, Muddassir Syed, Melanie Woods, Ganiraju Manyam, Lawrence N. Kwong, Benny Johnson, Van K. Morris, Philip Jones, David G. Menter, Michael S. Lee, Scott Kopetz
Summary: This study evaluates the therapeutic efficacy and safety of combined MEK-CDK4/6 inhibition in RAS mutant colorectal cancer using patient-derived xenografts and clinical trials, identifies biomarkers of response, and uncovers targetable mechanisms of resistance.
Article
Chemistry, Medicinal
Aarion Romany, Ruibin Liu, Shaoqi Zhan, Joseph Clayton, Jana Shen
Summary: The ERK pathway is crucial in tumorigenesis and there is a need for novel covalent inhibitors due to limited efficacy of current noncovalent inhibitors approved by FDA. A systematic study revealed possible targets for the development of covalent inhibitors against ERK pathway kinases.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Oncology
Dana C. Borcherding, Neha Amin, Kevin He, Xiaochun Zhang, Yang Lyu, Carina Dehner, Himanshi Bhatia, Angad Gothra, Layla Daud, Peter Ruminski, Christine A. Pratilas, Kai Pollard, Taylor Sundby, Brigitte C. Widemann, Angela C. Hirbe
Summary: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with limited treatment options and poor survival rates. Inhibition of TYK2 has shown promising results in decreasing proliferation and inducing apoptosis in MPNST, making it a potential therapeutic target.
CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Sandra Pavicevic, Sophie Reichelt, Deniz Uluk, Isabella Lurje, Cornelius Engelmann, Dominik P. Modest, Uwe Pelzer, Felix Krenzien, Nathanael Raschzok, Christian Benzing, Igor M. Sauer, Sebastian Stintzing, Frank Tacke, Wenzel Schoening, Moritz Schmelzle, Johann Pratschke, Georg Lurje
Summary: Cholangiocarcinoma is a rapidly increasing global malignancy of the biliary tract, often presenting with advanced or unresectable disease. Biomarkers obtained from patients' serum or tumor tissue could help guide therapy and identify those at higher risk of recurrence. Genetic aberrations in cholangiocarcinoma have also been linked with improved response to targeted therapies. This review provides an overview of prognostic and predictive biomarkers in cholangiocarcinoma.
Article
Cell Biology
Clara Alcon, Fernando Martin, Estela Prada, Jaume Mora, Aroa Soriano, Gabriela Guillen, Soledad Gallego, Josep Roma, Josep Samitier, Alberto Villanueva, Joan Montero
Summary: In this study, dynamic BH3 profiling was used to investigate the effectiveness of targeted agents and anti-apoptotic adaptations in rhabdomyosarcoma. The combination of a BH3 mimetic targeting MCL-1 and the MEK1/2 inhibitor trametinib was found to improve efficiency in rhabdomyosarcoma by blocking tumor adaptation to treatment.
CELL DEATH DISCOVERY
(2022)
Article
Multidisciplinary Sciences
Christopher P. Vellano, Michael G. White, Miles C. Andrews, Manoj Chelvanambi, Russell G. Witt, Joseph R. Daniele, Mark Titus, Jennifer L. McQuade, Fabio Conforti, Elizabeth M. Burton, Matthew J. Lastrapes, Gabriel Ologun, Alexandria P. Cogdill, Golnaz Morad, Peter Prieto, Alexander J. Lazar, Yanshuo Chu, Guangchun Han, M. A. Wadud Khan, Beth Helmink, Michael A. Davies, Rodabe N. Amaria, Jeffrey J. Kovacs, Scott E. Woodman, Sapna Patel, Patrick Hwu, Michael Peoples, Jeffrey E. Lee, Zachary A. Cooper, Haifeng Zhu, Guang Gao, Hiya Banerjee, Mike Lau, Jeffrey E. Gershenwald, Anthony Lucci, Emily Z. Keung, Merrick Ross, Laura Pala, Eleonora Pagan, Rossana Lazcano Segura, Qian Liu, Mikayla S. Borthwick, Eric Lau, Melinda S. Yates, Shannon N. Westin, Khalida Wani, Michael T. Tetzlaff, Lauren E. Haydu, Mikhila Mahendra, XiaoYan Ma, Christopher Logothetis, Zachary Kulstad, Sarah Johnson, Courtney W. Hudgens, Ningping Feng, Lorenzo Federico, Georgina Long, P. Andrew Futreal, Swathi Arur, Hussein A. Tawbi, Amy E. Moran, Linghua Wang, Timothy P. Heffernan, Joseph R. Marszalek, Jennifer A. Wargo
Summary: Treatment with neoadjuvant BRAF/MEK-targeted therapy showed improved outcomes in female patients compared to male patients in melanoma. Preclinical studies revealed impaired tumour activity in male mice after treatment, with higher androgen receptor expression. Pharmacological inhibition of androgen receptor signalling improved treatment responses in male and female mice, while induction of androgen receptor signalling impaired responses in male and female patients.
Article
Multidisciplinary Sciences
Federica Verginelli, Alberto Pisacane, Gennaro Gambardella, Antonio D'Ambrosio, Ermes Candiello, Marco Ferrio, Mara Panero, Laura Casorzo, Silvia Benvenuti, Eliano Cascardi, Rebecca Senetta, Elena Geuna, Andrea Ballabio, Filippo Montemurro, Anna Sapino, Paolo M. Comoglio, Carla Boccaccio
Summary: Cancer of Unknown Primary (CUP) is a mysterious and fatal disease characterized by metastatic spread without a known primary tumor. By studying cancer stem cells in CUP, it has been found that self-sustained propagation and sensitivity to MEK inhibition are common features of CUP.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Delphine Morales, Pascale Vigneron, Ines Ferreira, Warda Hamitou, Mikael Magnano, Laxsika Mahenthiran, Catherine Lok, Muriel Vayssade
Summary: Preclinical 3D in vitro coculture models closely mimic the physiological environment and are ideal for studying cellular interactions modulating cell sensitivity to drugs. Comparing the influence of conditioned media obtained from healthy or cancer-associated fibroblasts on the response of metastatic melanomas to the drugs, it was found that normal fibroblast supernatants potentiate the therapy's efficiency, while cancer-associated fibroblast secretomes favor melanoma cell survival.
Article
Oncology
Amanda N. Ruggieri, Mark Yarchoan, Subir Goyal, Yuan Liu, Elad Sharon, Helen X. Chen, Brian M. Olson, Chrystal M. Paulos, Bassel F. El-Rayes, Shishir K. Maithel, Nilofer S. Azad, Gregory B. Lesinski
Summary: This study provides a comprehensive analysis of peripheral immune features in patients with advanced biliary tract cancers (BTC) and their response to dual MEK/PD-L1 inhibition. The findings suggest that this treatment approach can improve clinical outcomes for patients with advanced BTC.
CLINICAL CANCER 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.
Article
Endocrinology & Metabolism
Francesco Calvanese, Timothee Jacquesson, Romain Manet, Alexandre Vasiljevic, Helene Lasolle, Francois Ducray, Gerald Raverot, Emmanuel Jouanneau
Summary: The study presented two cases of tubero-infundibular and ventricular Papillary Craniopharyngiomas treated with BRAF/MEK inhibitor therapy, resulting in a 90% reduction in tumor volume after neoadjuvant or adjuvant treatment. Both patients experienced minimal long-term morbidity after the targeted therapy and adjuvant radiotherapy. These findings suggest that confirmation of BRAFV600E mutation in Craniopharyngiomas and targeted therapy may provide improved long-term outcomes for patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Liang Yan, Bo Tu, Jun Yao, Jing Gong, Alessandro Carugo, Christopher A. Bristow, Qiuyun Wang, Cihui Zhu, Bingbing Dai, Ya'an Kang, Leng Han, Ningping Feng, Yanqing Jin, Jason Fleming, Timothy P. Heffernan, Wantong Yao, Haoqiang Ying
Summary: The study highlights the critical role of glucose metabolism in resistance to MAPK inhibition in KRAS-driven pancreatic cancer, suggesting a potential therapeutic approach in targeting this aggressive disease.
Article
Multidisciplinary Sciences
Marta Nyakas, Karianne Giller Fleten, Mads Haugland Haugen, Nikolai Engedal, Christina Sveen, Inger Nina Farstad, Vivi Ann Florenes, Lina Prasmickaite, Gunhild Mari Maelandsmo, Kotryna Seip
Summary: This study investigated the therapeutic potential of combining an AXL inhibitor (AXLi) and a clinically relevant BRAF inhibitor (BRAFi) for the treatment of metastatic melanoma. The results showed that AXL was expressed in the majority of melanoma lymph node metastases. In vitro experiments demonstrated that the combination of AXLi and BRAFi resulted in the largest reduction in cell viability. Moreover, pre-clinical studies using AXL(high) melanoma models showed a therapeutic benefit of adding AXLi to the BRAF-targeted therapy. Mechanistic insights revealed that AXLi potentiated BRAFi-induced apoptosis, stimulated ferroptosis, and inhibited autophagy. Overall, this study suggests that combining AXLi with standard therapy could improve the therapeutic outcome in metastatic melanoma.
SCIENTIFIC REPORTS
(2022)