Accounting for 10-20% of breast cancer cases, triple-negative breast cancer (TNBC) is associated with a disproportionate number of breast cancer deaths. One challenge in studying TNBC is its genomic profile: with the exception of TP53 loss, most breast cancer tumors are characterized by a high number of copy number alterations (CNAs), making modeling the disease in whole animals challenging. We computationally analyzed 186 CNA regions previously identified in breast cancer tumors to rank genes within each region by likelihood of acting as a tumor driver.
View Article and Find Full Text PDFApproximately 40% of colorectal cancer (CRC) cases are characterized by KRAS mutations, rendering them insensitive to most CRC therapies. While the reasons for this resistance remain incompletely understood, one key aspect is genetic complexity: in CRC, oncogenic KRAS is most commonly paired with mutations that alter WNT and P53 activities ("RAP"). Here, we demonstrate that elevated WNT activity upregulates canonical (NF-κB) signalling in both and human RAS mutant tumours.
View Article and Find Full Text PDFColorectal cancer (CRC) is the second most deadly cancer worldwide. One key reason is the failure of therapies that target RAS proteins, which represent approximately 40% of CRC cases. Despite the recent discovery of multiple alternative signalling pathways that contribute to resistance, durable therapies remain an unmet need.
View Article and Find Full Text PDFThroughout an individual's life, somatic cells acquire cancer-associated mutations. A fraction of these mutations trigger tumour formation, a phenomenon partly driven by the interplay of mutant and wild-type cell clones competing for dominance; conversely, other mutations function against tumour initiation. This mechanism of 'cell competition', can shift clone dynamics by evaluating the relative status of clonal populations, promoting 'winners' and eliminating 'losers'.
View Article and Find Full Text PDFBackground: People with mental health (MH) and substance use disorders (SUD) have high rates of tobacco use and tobacco-related mortality. They want to stop smoking and studies have shown they can quit, but few behavioral health facilities provide tobacco treatment. The purpose of this paper is to describe how a midwestern statewide behavioral health collaboration used regional data to pinpoint strengths and weaknesses in tobacco treatment trends, identified policies in neighboring states that were associated with high rates of tobacco treatment, and worked with state leaders to implement these policies to enhance treatment.
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