A5034340028- Glioma Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- Melanoma and MAPK Pathways
- Cancer Treatment and Pharmacology
- Cancer Research and Treatments
- Retinal Imaging and Analysis
- RNA modifications and cancer
- Retinal Diseases and Treatments
- Education and Learning Interventions
- Technology Use by Older Adults
- Ophthalmology and Visual Impairment Studies
- Subtitles and Audiovisual Media
University of Michigan
2017-2024
Michigan United
2024
Despite tremendous progress in precision oncology, adaptive resistance mechanisms limit the long-term effectiveness of molecularly targeted agents. Here we evaluated pharmacological profile MTX-531 that was computationally designed to selectively target two key drivers, epidermal growth factor receptor and phosphatidylinositol 3-OH kinase (PI3K). exhibits low-nanomolar potency against both targets with a high degree specificity predicted by cocrystal structural analyses. monotherapy...
Abstract Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), high-grade pediatric tumor the brain stem. In nearly all patients, available therapies fail prevent progression. Innovative combinatorial that penetrate blood–brain barrier and lead long-term control growth are desperately needed. We identified mechanisms radiotherapy, standard care for DIPG. On basis these findings, we rationally designed brain-penetrant...
Abstract Adaptive resistance mechanisms compromise the long-term effectiveness of kinase-targeted agents dictating need for strategic combination approaches. MTX-531 was computationally designed to selectively target both PI3K and wild type EGFR. exhibits low nanomolar potency against isoform family EGFR with a high degree specificity predicted by co-crystal structural analyses. Full kinome screening confirmed that is exquisitely selective its intended targets. We evaluated pharmacological...
Abstract Agents targeting epidermal growth factor receptor (EGFR) have met with limited success in the clinical management of colorectal cancer (CRC). Mutations KRAS, BRAF, and PIK3CA are important drivers resistance to EGFR-targeted therapy. Conversely, EGFR-mediated feedback mechanisms serve mediate MEK inhibitor-based treatment CRC by reactivating MAP kinase signaling. Our central hypothesis is that a dual small molecule inhibitor potently selectively targets only EGFR PI3KA, when...
<p>Supplemental Tables 1, 2, 3</p>
<div>Abstract<p>Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), high-grade pediatric tumor the brain stem. In nearly all patients, available therapies fail prevent progression. Innovative combinatorial that penetrate blood–brain barrier and lead long-term control growth are desperately needed. We identified mechanisms radiotherapy, standard care for DIPG. On basis these findings, we rationally designed...
<p>Supplemental Methods, Synthesis</p>
<p>Supplemental Figures 1, 2</p>
<p>Supplemental Tables 1, 2, 3</p>
<p>Supplemental Methods, Synthesis</p>
<p>Supplemental Figures 1, 2</p>
<div>Abstract<p>Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), high-grade pediatric tumor the brain stem. In nearly all patients, available therapies fail prevent progression. Innovative combinatorial that penetrate blood–brain barrier and lead long-term control growth are desperately needed. We identified mechanisms radiotherapy, standard care for DIPG. On basis these findings, we rationally designed...
Abstract Background Visual impairment (VI) is common in older adults and associated with adverse health outcomes. However, the association between objectively assessed VI recurrent hospitalization remains unclear. Objective To investigate of different domains visual function United States. Methods We used data from Round 11 National Health Aging Trends Study (NHATS), a nationally representative survey Medicare beneficiaries, which included objective measures distance near acuity contrast...
Abstract Internet is increasingly used by older adults for communication, socialization, household tasks, and health information/care. Although the internet most often accessed visual means, little known about whether vision impairment associated with use in adults. To address this question, we nationally representative data from round 12 (collected 2022) of National Health Aging Trends Study (NHATS), which included measures function (distance acuity, near contrast sensitivity) a series...
Abstract Pancreatic cancer is one of the deadliest forms cancer, with median 5-year survival rates less than 10%. This disease recalcitrant to chemotherapeutic approaches and recently approved therapies afford only modest improvements in survival. KRAS most commonly mutated gene pancreatic tumors an incidence rate exceeding 90%. Despite intensive efforts, has remained undruggable. Kinases acting both upstream downstream RAS continue be exploited for development novel agents attenuate...
Abstract Therapeutic resistance remains a major obstacle to successful clinical management of Diffuse Intrinsic Pontine Glioma (DIPG), high-grade pediatric tumor the brain stem. In nearly all patients, available therapies fail prevent progression. Innovative combinatorial that penetrate blood-brain barrier and lead long-term control growth are desperately needed. We identified mechanisms radiotherapy, standard care for DIPG. Based on these findings, we rationally designed brain-penetrant...
Abstract Therapeutic resistance remains a major obstacle to successful clinical management of Diffuse Intrinsic Pontine Glioma (DIPG), high-grade pediatric tumor the brain stem. In nearly all patients, available therapies fail prevent progression. Innovative combinatorial that penetrate blood-brain barrier and lead long-term control growth are desperately needed. We identified mechanisms radiotherapy, standard care for DIPG. Based on these findings, we rationally designed brain-penetrant...
Abstract Therapeutic resistance remains a major obstacle in the successful clinical management of Diffuse Intrinsic Pontine Glioma (DIPG), high-grade pediatric tumor arising brain stem. Currently available therapies do not prevent recurrence nearly all patients diagnosed with this devastating disease. Innovative combinatorial that penetrate blood barrier and effectively lead to long-term control growth are desperately needed. Using RNA sequencing, we identified mechanisms DIPG radiotherapy...