Summary of project PR001983
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001983. The data can be accessed directly via it's Project DOI: 10.21228/M8D72S This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001983 |
| Project DOI: | doi: 10.21228/M8D72S |
| Project Title: | A multimodal drug-diet-immunotherapy combination restrains melanoma progression and metastasis |
| Project Summary: | The genetic landscape of cancer cells can lead to specific metabolic dependencies for tumor growth. Dietary interventions represent an attractive strategy to restrict the availability of key nutrients to tumors. In this study, we identified that growth of a subset of melanoma was severely restricted by a rationally designed combination therapy of a stearoyl-CoA desaturase (SCD) inhibitor with an isocaloric low-oleic acid diet. Despite its importance in oncogenesis, SCD underwent monoallelic co-deletion along with PTEN on chromosome 10q in about 47.5% of melanoma, and the other SCD allele was methylated, resulting in very low SCD expression. While this SCD deficient subset was refractory to SCD inhibitors, the subset of PTEN wildtype melanoma that retained SCD was sensitive. As dietary oleic acid could potentially blunt the effect of SCD inhibitors, a low-oleic acid custom diet was combined with SCD inhibitor. The combination reduced monounsaturated fatty acids and increased saturated fatty acids, inducing robust apoptosis and growth suppression and inhibiting lung metastasis with minimal toxicity in preclinical mouse models of PTEN wildtype melanoma. When combined with anti-PD1 immunotherapy, the SCD inhibitor improved T cell functionality and further constrained melanoma growth in mice. Collectively, these results suggest that optimizing SCD inhibitors with diets low in oleic acid may offer a viable and efficacious therapeutic approach for improving melanoma treatment. |
| Institute: | University of Colorado Anschutz Medical Campus |
| Laboratory: | Lab of Angelo D'Alessandro in collaboration with lab of Biplab Dasgupta |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
Summary of all studies in project PR001983
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003184 | A multimodal drug-diet-immunotherapy combination restrains melanoma progression and metastasis - tumor lipidomics | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-05-18 | 1 | 20 | Uploaded data (4.8G)* |
| ST003185 | A multimodal drug-diet-immunotherapy combination restrains melanoma progression and metastasis - plasma lipidomics | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2024-05-18 | 1 | 24 | Uploaded data (6G)* |
