Deep molecular and cellular profiling of colorectal cancer tumor and immune microenvironment in alaska native people
Active Project Grant Awarded Last action
- Award ID
- R01CA280639
- Recipient
-
Fred Hutchinson Cancer Center UEI TJFZLPP6NYL6
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,477,285
Award facts
- Assistance listing
- 93.393 Cancer Cause and Prevention Research
- Completion date 69% complete
- Place of performance
- Seattle, WA 98109, USA
Award details come from USAspending.gov.
Description
- Abstract
- Alaska native people have the highest incidence and mortality rates of colorectal cancer (CRC) globally, with rates that are more than double those observed in the general U.S. Population (incidence: 89.0 VS. 38.6/100,000; mortality: 39.6/100,000 VS. 13.8/100,000). These high rates cannot be explained by access to screening, as dedicated efforts to increase CRC screening have resulted in screening rates in alaska native people that are comparable to the US average. These disparities have persisted for over 40 years and are of noted concern to community members and tribal health leaders alike, making this a priority research area for alaska native people. A key knowledge GAP is the lack of sizable and comprehensive studies characterizing the molecular features of colorectal tumors in alaska native patients. Accordingly, we propose an integrative approach to better understand CRC tumorigenesis and molecular subtypes in this high-risk population, and to evaluate whether various tumor and tumor microenvironment features contribute to disease progression. Specifically, we aim to deeply characterize the mutational, transcriptional, and cellular landscapes of CRC tumors and their immune microenvironments in 500 alaska native patients and link these characteristics to CRC-specific mortality. We will build on our existing collaboration between the alaska native tribal health consortium (anthc) and the fred hutchinson cancer center. We will capitalize on anthc's unique biorepository (linkable to comprehensive medical records) that contains tumor tissue samples of the majority of alaska native CRC patients diagnosed in alaska. Pilot data generated using biospecimens from this resource and utilizing the same platforms as proposed here demonstrate high-quality data and ensure that IRB and tribal approvals are in place to enable rapid execution of the proposed work. To identify clinically meaningful population differences, we will compare molecular profiles with those from non-hispanic white CRC patients using available data. In aim 1, we will perform whole-exome sequencing of CRC tumors and paired normal samples to identify driver genes and clinically actionable mutations particularly relevant to the alaska native population. To gain etiological insight, we will analyze mutational signatures that may be linked to environmental exposures and identify germline mutations in high-penetrance CRC risk genes to investigate their role in the increased CRC risk in alaska native people. In aim 2, we will apply two complementary cutting-edge spatial profiling technologies to fully characterize the tumoral immune response and discover mechanisms of immune evasion. We will perform spatial whole transcriptome profiling of CRC tumors using nanostring's geomx digital spatial profiling technology. We will use akoya biosciences' phenocycler platform for spatially resolved single immune cell phenotyping. We expect that insights gained through this work can inform the development of high-value, novel therapeutic strategies. In aim 3, we will leverage these molecular data to develop novel predictors of CRC-specific mortality that could help guide clinical decision making, improve outcomes, and reduce long-standing disparities.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $705,202 | |
| Amendment | $700,504 | |
| Amendment | $661,051 | |
| Amendment | $705,264 | |
| Original award | $705,264 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Alaska Native Tribal Health Consortium | $47,352 | |
| Alaska Native Tribal Health Consortium | $55,895 | |
| Alaska Native Tribal Health Consortium | $61,822 |
Quick answers
Who received award R01CA280639?
R01CA280639 was awarded to Fred Hutchinson Cancer Center by National Cancer Institute (National Institutes of Health) on May 25, 2023.
How much is award R01CA280639 worth?
$3,477,285 has been obligated on R01CA280639.
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