Publications by authors named "Mariusz Shrestha"
Article Synopsis
- The spread of tumor cells to essential organs significantly contributes to cancer-related deaths.
- This process, known as metastasis, complicates the treatment and management of various cancers.
- Understanding the mechanisms behind this spread is crucial for developing better therapies to improve patient outcomes.
Article Synopsis
- - The study investigates the differences in cancer drivers between primary and metastatic breast cancer using genetic techniques in female mice, focusing on mutations involving the Rb gene, which is often inactive in this type of cancer.
- - Researchers identified specific gene insertion sites (gCIS) that are linked to either primary tumors, metastases, or both, highlighting significant networks related to cancer progression, including a shared MET-RAS network and additional pathways for metastatic cancer.
- - Analysis of human clinical data reveals that certain genetic factors are more prevalent in primary tumors or metastases, suggesting targeted treatments that inhibit specific signaling pathways (like RB1, MET, and RHO) could help block tumor cell migration and improve outcomes for metastatic breast cancer patients.
Immune-checkpoint (IC) modulators like the poliovirus receptor (PVR) and programmed death ligand 1 (PD-L1) attenuate innate and adaptive immune responses and are potential therapeutic targets for diverse malignancies, including triple-negative breast cancer (TNBC). The retinoblastoma tumor suppressor, pRB, controls cell growth through E2F1-3 transcription factors, and its inactivation drives metastatic cancer, yet its effect on IC modulators is contentious. Here, we show that RB-loss and high E2F1/E2F2 signatures correlate with expression of PVR, CD274 (PD-L1 gene) and other IC modulators and that pRB represses whereas RB depletion and E2F1 induce PVR and CD274 in TNBC cells.
View Article and Find Full Text PDFNext-generation sequencing is a superior method for detecting known and novel RNA fusions in formalin-fixed, paraffin-embedded tissue over fluorescence in situ hybridization and RT-PCR. However, confidence in fusion calling and true negatives may be compromised by poor RNA quality. Using a commercial panel of 507 genes and the recommended 3-million read threshold to accept results, two cases yielded false negatives while exceeding this recommendation during clinical validation.
View Article and Find Full Text PDFBackground: MDM2 is elevated in multiple myeloma (MM). Although traditionally, MDM2 negatively regulates p53, a growing body of research suggests that MDM2 plays several p53-independent roles in cancer pathogenesis as a regulator of oncogene mRNA stability and translation. Yet, the molecular mechanisms underlying MDM2 overexpression and its role in drug resistance in MM remain undefined.
View Article and Find Full Text PDFArticle Synopsis
- CDC25 is a dual phosphatase that has been identified as a key target for various triple-negative breast cancers, especially those lacking certain genetic features.
- Inhibitors that block CDC25 show promising results when combined with PI3K inhibitors, leading to better suppression of tumor growth.
- The text highlights the potential of CDC25 inhibitors in cancer treatment while also addressing the challenges of making these treatments available in clinical settings.
Article Synopsis
- * In triple-negative breast cancer (TNBC), RB1 is often inactivated alongside PTEN and TP53, leading researchers to conduct inhibitor screens on cell lines that lack these tumor suppressors.
- * The study identified CDC25 phosphatase as a promising therapeutic target, showing that inhibiting CDC25 can suppress the growth of RB1-deficient TNBC cells, especially when combined with WEE1 and PI3K inhibitors.
Article Synopsis
- A key feature of cancer is the switch from catabolic to anabolic metabolism, allowing for rapid cell growth, influenced by mutations like PIK3CA and loss of tumor suppressors such as TP53 and RB1.
- Tumor development relies on active mitochondrial function and oxidative phosphorylation (OXPHOS), which has been shown to be enhanced by RB1 loss in breast cancer.
- The paper suggests that targeting both anabolic metabolism and OXPHOS could provide a therapeutic strategy against aggressive tumors that utilize lethal combinations of oncogenes and tumor suppressors.
Triple-negative breast cancer (TNBC) includes basal-like and claudin-low subtypes for which no specific treatment is currently available. Although the retinoblastoma tumor-suppressor gene (RB1) is frequently lost together with TP53 in TNBC, it is not directly targetable. There is thus great interest in identifying vulnerabilities downstream of RB1 that can be therapeutically exploited.
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