Unlabelled: KRAS inhibitors have demonstrated exciting preclinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KrasG12D, p53-mutant, murine pancreatic ductal adenocarcinoma-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intratumoral CD8+ T cells without durable responses.
View Article and Find Full Text PDFThe AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2.
View Article and Find Full Text PDFPurpose: Endocrine therapy resistance (ETR) remains the greatest challenge in treating patients with hormone receptor-positive breast cancer. We set out to identify molecular mechanisms underlying ETR through in-depth genomic analysis of breast tumors.
Experimental Design: We collected pre-treatment and sequential on-treatment tumor samples from 35 patients with estrogen receptor-positive breast cancer treated with neoadjuvant then adjuvant endocrine therapy; 3 had intrinsic resistance, 19 acquired resistance, and 13 remained sensitive.
Breast cancer is classified into multiple distinct histologic types, and many of the rarer types have limited characterization. Here, we extend The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset with additional histologic type annotations, in a total of 1063 breast cancers. We analyze this extended dataset to define transcriptomic and genomic profiles of six rare special histologic types: cribriform, micropapillary, mucinous, papillary, metaplastic, and invasive carcinoma with medullary pattern.
View Article and Find Full Text PDFPeritoneal adhesion occurs in a majority of patients following abdominal surgery and can result in significant side effects and complications. Current strategies to minimize adhesions involve the use of nontargeted anatomical barriers that are either inefficient in protecting injured areas or lacking the adequate residence time to prevent adhesions. Herein, the development of a biologically targeted photo-crosslinkable nanopatch (pCNP) is reported that can prevent postsurgical adhesion.
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