Publications by authors named "Riley A Hampsch"
Article Synopsis
- Estrogen receptor-positive (ER+) breast cancers often recur due to undetectable persister cancer cells that survive endocrine treatments, necessitating new strategies to target these cells and prevent recurrence.
- Researchers used CRISPR-Cas9 screening to discover that these persister cells rely on mitochondrial respiration instead of glycolysis for energy, indicating a unique metabolic mechanism.
- A clinical trial revealed that tumors with residual cells after endocrine therapy showed increased mitochondrial content, suggesting that targeting mitochondrial metabolism could enhance treatment effectiveness against these resilient cancer cells.
Aim: Metformin is used for the management of type 2 diabetes mellitus (T2DM) and is being tested clinically as an anticancer agent. Metformin concentrations safely achievable in human solid tissues including tumours are unknown. This study was designed to determine metformin concentration in tissue compartments as a function of dose to inform rational dosing in preclinical models and interpretation of clinical results.
View Article and Find Full Text PDFPurpose: Despite adjuvant endocrine therapy for patients with estrogen receptor alpha (ER)-positive breast cancer, dormant residual disease can persist for years and eventually cause tumor recurrence. We sought to deduce mechanisms underlying the persistence of dormant cancer cells to identify therapeutic strategies.
Experimental Design: Mimicking the aromatase inhibitor-induced depletion of estrogen levels used to treat patients, we developed preclinical models of dormancy in ER breast cancer induced by estrogen withdrawal in mice.
Article Synopsis
- The study hypothesized that analyzing different cancer types together could reveal new subgroups with specific treatment weaknesses, focusing on breast and ovarian cancers due to their molecular similarities.
- Researchers used data analysis to identify cancer subgroups and tested their sensitivity to Hsp90 inhibitors (Hsp90i), validating results with various models.
- Results showed that a specific subgroup, mainly composed of triple-negative breast and certain ovarian cancers, was more susceptible to Hsp90i treatment, suggesting gene expression profiles could help identify targeted therapies for these cancers.
Estrogens have been shown to elicit anticancer effects against estrogen receptor α (ER)-positive breast cancer. We sought to determine the mechanism underlying the therapeutic response. Response to 17β-estradiol was assessed in ER+ breast cancer models with resistance to estrogen deprivation: WHIM16 patient-derived xenografts, C7-2-HI and C4-HI murine mammary adenocarcinomas, and long-term estrogen-deprived MCF-7 cells.
View Article and Find Full Text PDFDrug resistance to approved systemic therapies in estrogen receptor-positive (ER+) breast cancer remains common. We hypothesized that factors present in the human tumor microenvironment (TME) drive drug resistance. Screening of a library of recombinant secreted microenvironmental proteins revealed fibroblast growth factor 2 (FGF2) as a potent mediator of resistance to anti-estrogens, mTORC1 inhibition, and phosphatidylinositol 3-kinase inhibition in ER+ breast cancer.
View Article and Find Full Text PDFRac GTPases have oncogenic roles in cell growth, survival, and migration. We tested response to the Rac inhibitor EHT1864 in a panel of breast cancer cell lines. EHT1864-induced growth inhibition was associated with dual inhibition of the PI3K/AKT/mTORC1 and MEK/ERK pathways.
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