Publications by authors named "Alexandria L Fink"
Article Synopsis
- Primary central nervous system lymphoma (PCNSL) is a severe type of brain lymphoma with poor outcomes despite aggressive treatment; recent studies have identified key genetic mutations linked to its development, particularly in immunocompetent and Epstein-Barr virus-positive patients.* -
- The research established 12 patient-derived xenograft (PDX) models that retained the essential characteristics of PCNSL, confirming the presence of specific mutations in patient samples and highlighting a common deregulated signaling pathway (RelA/p65-hexokinase 2) that contributes to tumor growth.* -
- These PDX models provide a valuable tool for testing new treatments and understanding the disease's mechanisms, focusing on the hyperactive signaling axis as a potential
Purpose: Oligodendroglioma has a relatively favorable prognosis, however, often undergoes malignant progression. We hypothesized that preclinical models of oligodendroglioma could facilitate identification of therapeutic targets in progressive oligodendroglioma. We established multiple oligodendroglioma xenografts to determine if the PI3K/AKT/mTOR signaling pathway drives tumor progression.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates GDC-0084, a dual PI3K/mTOR inhibitor, for treating breast cancer brain metastases, particularly focusing on its effectiveness against cells with specific mutations.
- Results show that GDC-0084 significantly reduces cell viability and induces apoptosis in mutant breast cancer cell lines, but only leads to growth inhibition in wild-type cell lines.
- Findings suggest that GDC-0084 could be a promising treatment for breast cancer brain metastases with certain genetic mutations, and a national clinical trial is proposed to explore its clinical potential further.
Background: Papillary craniopharyngiomas are characterized by BRAFV600E mutations. Targeted therapy can elicit a dramatic radiographic regression of these tumors. Therefore, prediction of BRAF mutation status before definitive surgery could enable neoadjuvant treatment strategies.
View Article and Find Full Text PDFMismatch repair (MMR) deficiency through inactivation has been identified in up to 30% of recurrent high-grade gliomas, and represents a key molecular mechanism underlying the acquired resistance to the alkylating agent temozolomide (TMZ). To develop a therapeutic strategy that could be effective in these TMZ-refractory gliomas, we first screened 13 DNA damage response modulators for their ability to suppress viability of MSH6-inactivated, TMZ-resistant glioma cells. We identified a PLK1 selective inhibitor, Volasertib, as the most potent in inhibiting proliferation of glioblastoma cells.
View Article and Find Full Text PDFProgressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples.
View Article and Find Full Text PDFAggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. However, progression in many of these patients is characterized by local regrowth. Most lower-grade gliomas harbor isocitrate dehydrogenase 1 () or mutations, which sensitize to metabolism-altering agents.
View Article and Find Full Text PDF