Publications by authors named "L E Dobrolecki"
Combination chemotherapy remains essential for clinical management of triple-negative breast cancer (TNBC). Consequently, responses to multiple single agents cannot be delineated at the single patient level, even though some patients might not require all drugs in the combination. Herein, we conduct multi-omic analyses of orthotopic TNBC patient-derived xenografts (PDXs) treated with single agent carboplatin, docetaxel, or the combination.
View Article and Find Full Text PDFTherapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells.
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- Chemotherapy combined with immune checkpoint inhibitors (ICIs) is used to boost immunotherapy effectiveness, but certain tumors, especially triple-negative breast cancer (TNBC), often remain unresponsive.
- The study identifies IRE1α, an ER stress sensor, as a key factor that limits the immune-boosting effects of taxane chemotherapy in these tumors by silencing double-stranded RNA (dsRNA) and preventing a type of inflammatory cell death called pyroptosis.
- Inhibiting IRE1α allows taxane to produce more dsRNA, which activates immune responses, transforming PD-L1-negative TNBC tumors into ones that are sensitive to immunotherapy.
Article Synopsis
- Mitochondria are important parts of cells that help with energy and can influence cancer growth and how well treatments work.
- Researchers studied a type of aggressive breast cancer called triple negative breast cancer (TNBC) to understand how the structure of mitochondria changes when treated with chemotherapy.
- They found that chemotherapy can change the shape and size of mitochondria in tumors, differing in treated tumors compared to those that weren't treated, suggesting that understanding these changes could help improve cancer treatment strategies.
Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response.
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