20 research outputs found
Molecular heterogeneity and receptor coamplification drive resistance to targeted therapy in MET-Amplified esophagogastric cancer
Recommended from our members
Making Connections - Envisioning Springfield\u27s North End
This work explores a service learning strategy in the context of the senior Urban Design Studio taught in the Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst. The primary goal of this project is to stimulate a conversation in the neighborhoods of the North End, to develop green design strategies, to improve services and businesses for residents and the employees of local businesses, and to foster cultural engagement and interaction in the North End that will enhance the vibrancy, resilience, and quality of life of this urban community. Making connections - Envisioning Springfield\u27s North End proposes improved connectivity in a physical, cultural, and social sense will be key to attaining these goals and to engaging and synergizing individuals and community groups in the North End - residents, businesses, schools, churches, employers, and employees. Six sustainable learning and planning principles have emerged from this studio:
1. Input and interaction – Visioning workshops connect campus and community
2. Community-building art - Expression of place and people
3. Healthy living - Urban agriculture and education
4. Urban greenways – Abandoned railways and urban rivers and streams
5. Green infrastructure - Green streets as networks and structural framework
6. Sustainable urban form – Mixed use and pedestrian friendly neighborhood
Strategies for monitoring and combating resistance to combination kinase inhibitors for cancer therapy
Tumor heterogeneity and Lesion-Specific response to targeted therapy in colorectal cancer
Tumor heterogeneity and lesion-specific response to targeted therapy in colorectal cancer
How genomic heterogeneity associated with acquired resistance to targeted agents affects response to subsequent therapy is unknown. We studied EGFR blockade in colorectal cancer to assess whether tissue and liquid biopsies can be integrated with radiological imaging to monitor the impact of individual oncogenic alterations on lesion-specific responses. Biopsy of a patient's progressing liver metastasis following prolonged response to cetuximab revealed a K57T MEK1 mutation as a novel mechanism of acquired resistance. This lesion regressed upon treatment with panitumumab and the MEK inhibitor trametinib. In ctDNA, mutant MEK1 levels declined with treatment, but a previously unrecognized KRAS Q61H mutation was also identified that increased despite therapy. This same KRAS mutation was later found in a separate non-responding metastasis. In summary, parallel analyses of tumor biopsies and serial ctDNA monitoring show that lesion-specific radiographic responses to subsequent targeted therapies can be driven by distinct resistance mechanisms arising within separate tumor lesions in the same patient
Hotspot mutant p53-R273H inhibits KLF6 expression to promote cell migration and tumor metastasis
A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination
Cancer Genomics [version 1; referees: 2 approved]
Modern cancer genomics has emerged from the combination of the Human Genome Reference, massively parallel sequencing, and the comparison of tumor to normal DNA sequences, revealing novel insights into the cancer genome and its amazing diversity. Recent developments in applying our knowledge of cancer genomics have focused on the utility of these data for clinical applications. The emergent results of this translation into the clinical setting already are changing the clinical care and monitoring of cancer patients