MASSACHUSETTS GENERAL HOSPITAL, THE
Applying Genomics and Other High Throughput Technologies is the thematic area that this application addresses. Ovarian cancer is the most lethal gynecologic malignancy. It has a high response rate to initial combined platinum taxane chemotherapy following debulking surgery. However, the vast majority of these women will have their cancer recur within 12 to 24 months after diagnosis and will die of progressively chemotherapy-resistant tumor. No improvement has been made to improve overall survival over the past decade. Multiple prognostic and predictive markers were identified in the past few years but none of them have satisfactory predictive values. Using genomic technologies, we and others including the Cancer Genome Atlas Project have recently generated transcriptome signatures which purport to stratify patients according to
survival or predict response to chemotherapy. However, none of signatures have been validated on the transcript levels and only samples from a single institution were used for each study. The clinical significance of these profiles remains unknown. In this application, we propose to perform a comprehensive survey of published ovarian cancer signatures, including a cross-study validation using existing publicly available data, tuning of available signatures and validation of signatures using DASL technology on multi-center clinical trial GOG218 specimens. This approach will provide us with robust prognostic and predictive signatures, which will enable physicians to identify patients who will not respond to standard therapy, allow for the avoidance of unnecessary toxicity and the opportunity to be treated with experimental therapy. In addition, the signatures of resistance will certainly contain genes, which are functionally important to the resistant phenotype. These genes will be important therapeutic targets for the reversal of the resistant phenotype. We expect this proposal to radically change the clinical management of ovarian cancer patients, who should benefit greatly and immediately from the results of this project.
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| AWARD OVERVIEW |
| Award Number |
1RC4CA156551-01 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$3,723,748 |
Project Location - City |
Boston |
| Award Date |
09/27/2010 |
Project Location - State |
MA |
| Project Status |
More than 50% Completed |
Project Location - Zip |
02114-0000
|
| Jobs Reported |
4.63 |
Congressional District |
08 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
MASSACHUSETTS GENERAL HOSPITAL, THE |
| Recipient DUNS Number |
073130411
|
| Recipient Address |
55 FRUIT ST |
| Recipient City |
BOSTON |
| Recipient State |
Massachusetts |
| Recipient Zip |
02114-2621 |
| Recipient Congressional District |
08 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
Genomic Stratification of Ovarian Cancer Patients |
| Project Status |
More than 50% Completed |
| Final Project Report Submitted |
No |
| Project Activities Description |
General Medical and Surgical Hospitals |
| Quarterly Activities/Project Description |
Ovarian cancer is the most lethal gynecologic malignancy. It has a high response rate to initial
combined platinum taxane chemotherapy following debulking surgery. However, the vast majority of these
women will have their cancer recur within 12 to 24 months after diagnosis and will die of progressively
chemotherapy-resistant tumor. No improvement has been made to improve overall survival over the past
decade. Multiple prognostic and predictive markers were identified in the past few years but none of them
have satisfactory predictive values. Using genomic technologies, we and others including the Cancer Genome
Atlas Project have recently generated transcriptome signatures which purport to stratify patients according to survival or predict response to chemotherapy. However, none of signatures have been validated on the
transcript levels and only samples from a single institution were used for each study. The clinical significance of these profiles remains unknown. In this application, we propose to perform a comprehensive survey of published ovarian cancer signatures, including a cross-study validation using existing publicly available data,tuning of available signatures and validation of signatures using DASL technology on multi-center clinical trialGOG218 specimens. This approach will provide us with robust prognostic and predictive signatures, which will enable physicians to identify patients who will not respond to standard therapy, allow for the avoidance of unnecessary toxicity and the opportunity to be treated with experimental therapy. In addition, the signatures of resistance will certainly contain genes, which are functionally important to the resistant phenotype. These genes will be important therapeutic targets for the reversal of the resistant phenotype. We expect this research to radically change the clinical management of ovarian cancer patients, who should benefit greatly and immediately from the results of this project. |
| Jobs Created |
4.63 |
| Description of Jobs Created |
One position will be retained and 2 new positions will be filled. Co-Investigator, M. Birrer, M.D., Ph.D., 2.4 calendar months – Dr. Birrer is the Director of the Laboratory of Gynecologic Oncology at the Massachusetts General Hospital and Professor in the Department of Medicine, Harvard Medical School. Dr. Birrer will work closely with Drs. Mok and Parmigiani to ensure the smooth conduct of the project. Further, he will ensure that all timelines and delieverables are achieved. This will involve regular meetings, evaluation of results and trouble shooting. Dr Birrer will alos interact with the GOG tissue bank and the consultants on the project. Finally all of the DASL profiling will be done in Dr Birrer’s laboratory
Post doctoral fellow TBN will devote 12 calender months to the project. The fellow will be in charge of maintaining the iScan Core system. This will involve initial set-up, training and continula quality assurance of all of its components. Further, he will be responsible for the processing and image capture of all dasl arrays in this project
Post-doctoral fellow TBN will devote 12 calender months to the project. The fellow will receive microdissected nucleic acids from the MDACC laboratory of Dr Mok and perform quality assessments. The fellow will process them into Dasl probes for expression profiling. The fellow will perform all validation assays required in the project
|
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
75-0850 |
| Award Information |
| Award Date |
09/27/2010 |
| Award Number |
1RC4CA156551-01 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
75 |
| Funding Agency Name |
Department of Health and Human Services |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
75 |
| Awarding Agency Name |
Department of Health and Human Services |
| Amount of Award |
$3,723,748 |
| Funds Invoiced/Received |
$2,146,793 |
| Expenditure Amount |
$2,146,793 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
622110 |
| Activity Description |
General Medical and Surgical Hospitals |
| Sub-Awards Information |
| Sub-awards to Organizations |
2 |
| Sub-award Amounts to Organizations |
$4,291,766 |
| Sub-Awards to Individuals |
2 |
| Sub-Award Amounts to Individuals |
$2,145,883 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
1 |
| Total Amount of payments to vendors greater than $25,000/award |
$40,534 |
| Number of payments to vendors less than $25,000/award |
231 |
| Total Amount of payments to vendors less than $25,000/award |
$204,079 |
Sub-award 217168A - DANA-FARBER CANCER INSTITUTE, INC.
| Sub-Award Amount |
$2,851,556 |
| Sub-Award Date |
11/08/2010 |
| Sub-Awards Disbursed |
$737,255.84 |
| Project Location - City |
Boston |
| Project Location - State |
MA |
| Project Location - Zip Code |
02115-6013 |
| Project Location - Congressional District |
07 |
| Sub-Recipient DUNS Number |
076580745
|
| Sub-Recipient Address |
450 BROOKLINE AVE STE 30 |
| Sub-Recipient City |
BOSTON |
| Sub-Recipient State |
Massachusetts |
| Sub-Recipient Zip Code |
02115-6013 |
| Sub-Recipient Congressional District |
07 |
Required To Report Top 5
Highly Compensated Officials |
No |
Sub-award 217168B - UNIVERSITY OF TEXAS M D ANDERSON
| Sub-Award Amount |
$1,440,210 |
| Sub-Award Date |
11/18/2010 |
| Sub-Awards Disbursed |
$394,727.64 |
| Project Location - City |
HOUSTON |
| Project Location - State |
TX |
| Project Location - Zip Code |
77030-4009 |
| Project Location - Congressional District |
09 |
| Sub-Recipient DUNS Number |
800772139
|
| Sub-Recipient Address |
1515 HOLCOMBE BLVD UNIT 207 |
| Sub-Recipient City |
HOUSTON |
| Sub-Recipient State |
Texas |
| Sub-Recipient Zip Code |
77030-4009 |
| Sub-Recipient Congressional District |
09 |
Required To Report Top 5
Highly Compensated Officials |
No |
Harvard University - Award Number 1RC4CA156551-01 - Harvard University
| Award Number |
1RC4CA156551-01 |
| Sub-Award Number |
217168A |
| Vendor DUNS Number |
Not reported |
| Vendor HQ Zip Code + 4 |
02138-2901 |
| Vendor Name |
Harvard University |
| Product and Service Description |
billing arrangement for salary and fringe benefits |
| Payment Amount |
$40,534 |
| Location Information |
| Latitude, Longitude |
42º 21' 44",
-71º 4' 9" |
| Congressional District |
08 |
| Address 1 |
55 Fruit Street |
| Address 2 |
|
| City |
Boston |
| County |
Suffolk |
| State |
MA |
| Zip |
02114-0000 |
|
 |