Kenneth Chen
@kennethschen.bsky.social
210 followers 230 following 18 posts
Pediatric hematology/oncology, UT Southwestern | DICER1/DROSHA-driven childhood cancer | www.kennethchenlab.com
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Reposted by Kenneth Chen
kennethschen.bsky.social
Our study, led by Dr. Patricia Tiburcio, showed that blocking protein recycling may help fight anaplastic Wilms Tumor—a rare, aggressive childhood kidney cancer. Combining bortezomib with dactinomycin made tumors more sensitive to treatment in the lab. doi.org/10.1016/j.xc...
Blocking protein recycling may help fight anaplastic Wilms tumor.
kennethschen.bsky.social
Congratulations to Claudette Fraire, Kavita Desai, Indumathy Jagadeeswaran, and others, for their work showing how microRNA loss drives a mouse model of a childhood cancer called pineoblastoma! @genesdev.bsky.social genesdev.cshlp.org/cgi/content/...
Reposted by Kenneth Chen
theaacr.bsky.social
How can new approaches in early detection make a difference for pediatric cancers? In the new episode Believe in Progress podcast, we speak with Dr. Kris Ann P. Schultz, a pediatric oncologist, about how research is reshaping pediatric cancer care: www.youtube.com/playlist?lis...
kennethschen.bsky.social
This dashboard is great. Could you pin it to the top of your feed, or add the link to your profile?
Reposted by Kenneth Chen
Reposted by Kenneth Chen
Reposted by Kenneth Chen
ourworldindata.org
Childhood cancer deaths in the United States have declined six-fold over the last seventy years
This chart presents US cancer death rates in children under five years old, measured in reported annual death rates per 100,000 children. It consists of four graphs:

1. All Malignant Cancers Combined: This graph, shown in black, illustrates a decline in childhood cancer death rates from about 11 per 100,000 in 1950 to around 1.8 in 2021, indicating a six-fold decrease since the 1950s.
   
2. Leukemia: This graph shows a decrease from around 5 per 100,000 in 1950 to less than 1 in 2021, following a similar declining trend throughout the decades.

3. Brain and Nervous System Cancers: This chart shows some fluctuations but overall a decline from nearly 0.8 per 100,000 in 1950 to about 0.4 in 2021.

4. Lymphomas and Multiple Myeloma: This graph shows fluctuations and a decline from around 0.8 in the late 1950s to less than 0.2 by 2021.

The data is sourced from the WHO Mortality Database (2024), with a note indicating that figures may fluctuate year-by-year due to low numbers.
kennethschen.bsky.social
This was a collaborative team effort! Thanks to Kavita Desai, Patricia Tiburcio, Austin Warne, and everyone else! Thanks also to funding from Pablove Foundation, Alex's Lemonade Stand, CPRIT, and NIH. And thanks to mentorship and support from @amatrudalab.bsky.social!
kennethschen.bsky.social
So: Why haven't childhood cancers responded to ICIs?

Maybe we haven't been treating the right patients. The single-agent trials in pediatrics tested these drugs against all types of solid tumors. But we show that certain tumors are more immune-enriched.
kennethschen.bsky.social
Lastly, using public data from adult cancers, we showed that microRNA pathway alterations were linked to immune gene expression signatures and better response to ICIs.
kennethschen.bsky.social
The immune subset was also enriched for beta-catenin and microRNA pathway mutations. We verified that Wnt signaling induced PD-L1 expression in Wilms tumor cells. We also showed that knocking down DROSHA or DICER1 in Wilms tumor cells caused a robust increase in PD-L1.
kennethschen.bsky.social
Chemotherapy-treated tumors were in this immune subset. In public RNA-seq from an independent group of tumors, chemo exposure was also associated with immune gene expression. In the lab, we found that some chemotherapies, like doxorubicin, were particularly effective at inducing PD-L1.
kennethschen.bsky.social
We studied Wilms tumor, the most common childhood kidney cancer, which has low mutational burden. Using protein arrays, we were surprised to find that about a subset show upregulation of immune markers.
kennethschen.bsky.social
Thanks for including me!
Reposted by Kenneth Chen
olivier-saulnier.bsky.social
Let's build a starter pack for childhood cancer research.
Please send a message to be added! 🎗️
go.bsky.app/Tpd9QnM
Reposted by Kenneth Chen
mendell-lab.bsky.social
I’m thrilled to share a collaborative story from @Mendell_lab and Jan Erzberger labs, led by postdoc extraordinaire Xiaoqiang Zhu. We showed that in addition to their canonical decoding function, tRNAs play a key role in regulating mRNA stability during translation!
www.science.org/doi/10.1126/...
Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes
The CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation....
www.science.org