Publications by authors named "E C Petricoin"
Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR).
View Article and Find Full Text PDFDespite of massive emergence of molecular targeting drugs, the mainstay of advanced gastric cancer (GC) therapy is DNA-damaging drugs. Using a reverse-phase protein array-based proteogenomic analysis of a panel of 8 GC cell lines, we identified genetic alterations and signaling pathways, potentially associated with resistance to DNA-damaging drugs, including 5-fluorouracil (5FU), cisplatin, and etoposide. Resistance to cisplatin and etoposide, but not 5FU, was negatively associated with global copy number loss, vimentin expression, and caspase activity, which are considered hallmarks of previously established EMT subtype.
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- Glioblastoma (GBM) tumors show diverse genetic and transcriptional profiles, leading to significant variations in how cancer stem cells (CSCs) respond to standard treatments like radiation and temozolomide (TMZ).
- Through targeted proteomics and RNA sequencing, the study found that while differentiating CSCs to an astrocytic state activates certain oncogenic pathways and retains some "stemness," it also increases resistance to TMZ treatment.
- The transcriptional response to treatments was largely influenced by the p53 status of the cells, revealing that both mutant and wild-type p53 models activated a DNA-damage related immune response, indicating potential pathways for improving GBM treatment strategies.
Article Synopsis
- A phase II trial investigated the effectiveness of combining enzalutamide with fulvestrant in treating ER+/HER2- breast cancer to see if it reduces residual tumors at surgery compared to fulvestrant alone.
- * The combination treatment showed a significantly higher rate of achieving complete tumor response (PEPI=0) and improved immune activation in tumors compared to fulvestrant only.
- * Results indicated that the combination therapy not only lowered Ki67 levels (a marker for cancer proliferation) but also altered the tumor immune environment, suggesting increased anti-tumor activity.
Recent trials have shown the efficacy of trastuzumab deruxtecan (T-DXd) in HER2-negative patients, but there is not yet a way to identify which patients will best respond, especially with the inability of current HER2 IHC and FISH assays to accurately determine HER2 expression in the unamplified setting. Here, we present a heavily pre-treated patient with triple-negative breast cancer (HER2 IHC 0 who had a complete response to T-DXd. In this case, we used a CLIA-certified reverse-phase protein array-based proteomic assay (RPPA) to determine that the patient had moderate HER2 protein expression (HER2 2+, 42%) and activation (HER2 1+, 23%).
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