Wednesday, July 30, 2025 7/30/2025

PI3K/PTEN/Akt signaling and the genesis of cancer

Award Number: R01CA090764
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2001
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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PI3K/PTEN/Akt signaling and the genesis of cancer - This is the fourth competitive renewal of this grant application that was funded for the past 20 years. Over the years funding through this grant application led to several milestone observations and new discoveries. In the current grant application, we will follow intriguing observations made during the last period of funding. Our genetic studies in mice, using systemic deletion of Akt isoforms after tumor onset, recapitulate some of the adverse effects observed in patients after treatment with PI3K and Akt inhibitors such as hyperinsulinemia, and hyperglycemia, severe diarrhea, and liver damage. Our studies in mice could therefore provide mechanistic explanations for the adverse physiological consequences induced by PI3K and Akt inhibitors. Our results using mouse models of breast cancer and inducible systemic deletion of Akt isoforms after tumor onset to emulate drug therapy, suggest the followings: (i) Systemic Akt1 inhibition after tumor onset reduces metastasis by inhibiting tumor associate and pro-metastatic neutrophils. This is relevant to human breast cancer as high ratio of neutrophils to lymphocyte (NLR) is associated with worse overall survival and disease-free survival. (ii) Neutrophils’ specific deletion of Akt1 is sufficient to inhibit breast cancer metastasis. (iii) Specific Akt1 inhibitors could inhibit tumor progression and metastasis of Her2 enriched, Luminal B, and triple negative breast cancer. (iv) Systemic Akt1 inhibition prohibits breast cancer metastasis regardless of primary tumor type (Akt1 specific inhibitors should be developed). (v) Systemic Akt2 inhibition may not be beneficial for breast cancer therapy because of increased circulating levels of insulin and hyperactivation of the other Akt isoforms (drugs that inhibit Akt2 might be avoided). (vi) Pan-Akt inhibitors may not be effective unless they don’t inhibit Akt2 activity to a high extent. In the first part of the current grant application, we will investigate how tumor associated neutrophils are programmed by the tumors both transcriptionally and metabolically and how Akt1 deficiency impairs their ability to promote breast cancer metastasis. In the second part of the grant application will investigate mechanistically the adverse effects induced by pan-Akt or Akt2 inhibition and how to alleviate them. The long-term goal of this grant application is to establish the rationale for developing Akt1 specific inhibitors and enable the efficient use of Akt inhibitors for cancer and cancer metastasis therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $467,725 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	23	2/14/2025	NON-COMPETING CONTINUATION	$420,953
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	23	5/22/2025	NON-COMPETING CONTINUATION	$46,772
														Subtotal = $467,725

Issue Date FY: 2024 ( Subtotal = $444,339 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	002	22	4/16/2024	NON-COMPETING CONTINUATION	$23,386
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	22	2/2/2024	NON-COMPETING CONTINUATION	$420,953
2024	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	20	1/23/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $444,339

Issue Date FY: 2023 ( Subtotal = $467,549 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	21	2/13/2023	COMPETING CONTINUATION	$467,549
2023	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	20	2/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $467,549

Issue Date FY: 2021 ( Subtotal = $425,203 )
2021	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	20	3/2/2021	NON-COMPETING CONTINUATION	$425,203
														Subtotal = $425,203

Issue Date FY: 2020 ( Subtotal = $425,203 )
2020	2020	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	19	3/10/2020	NON-COMPETING CONTINUATION	$425,203
														Subtotal = $425,203

Issue Date FY: 2019 ( Subtotal = $412,448 )
2019	2019	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	18	3/7/2019	NON-COMPETING CONTINUATION	$412,448
														Subtotal = $412,448

Issue Date FY: 2018 ( Subtotal = $425,203 )
2018	2018	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	17	5/24/2018	NON-COMPETING CONTINUATION	$42,521
2018	2018	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	17	3/8/2018	NON-COMPETING CONTINUATION	$382,682
														Subtotal = $425,203

Issue Date FY: 2017 ( Subtotal = $366,329 )
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	16	3/16/2017	COMPETING CONTINUATION	$366,329
2017	2017	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	002	16	7/7/2017	COMPETING CONTINUATION	$6
2017	2015	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	15	7/7/2017	NON-COMPETING CONTINUATION	-$6
														Subtotal = $366,329

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2015	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	15	4/12/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $395,208 )
2015	2015	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	15	3/19/2015	NON-COMPETING CONTINUATION	$395,208
														Subtotal = $395,208

Issue Date FY: 2014 ( Subtotal = $379,662 )
2014	2014	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	14	3/20/2014	NON-COMPETING CONTINUATION	$379,662
														Subtotal = $379,662

Issue Date FY: 2013 ( Subtotal = $372,025 )
2013	2013	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	13	7/1/2013	NON-COMPETING CONTINUATION	$193,928
2013	2013	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	13	3/1/2013	NON-COMPETING CONTINUATION	$178,097
														Subtotal = $372,025

Issue Date FY: 2012 ( Subtotal = $394,577 )
2012	2012	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	12	3/21/2012	NON-COMPETING CONTINUATION	$394,577
														Subtotal = $394,577

Issue Date FY: 2011 ( Subtotal = $379,009 )
2011	2011	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	11	1/13/2011	COMPETING CONTINUATION	$360,059
2011	2011	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	001	11	6/30/2011	COMPETING CONTINUATION	$18,950
														Subtotal = $379,009

Issue Date FY: 2010 ( Subtotal = $370,234 )
2010	2010	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	10	3/26/2010	NON-COMPETING CONTINUATION	$370,234
														Subtotal = $370,234

Issue Date FY: 2009 ( Subtotal = $378,132 )
2009	2009	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	9	3/30/2009	NON-COMPETING CONTINUATION	$378,132
														Subtotal = $378,132

Issue Date FY: 2008 ( Subtotal = $367,867 )
2008	2008	UNIVERSITY OF ILLINOIS AT CHICAGO	890 SOUTH MARSHFIELD AVENUE	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	8	3/24/2008	NON-COMPETING CONTINUATION	$367,867
														Subtotal = $367,867

Issue Date FY: 2007 ( Subtotal = $364,986 )
2007	2007	UNIVERSITY OF ILLINOIS AT CHICAGO	809 S MARSHFIELD AVE, 511 MB	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	7	4/20/2007	NON-COMPETING CONTINUATION	$364,986
														Subtotal = $364,986

Issue Date FY: 2006 ( Subtotal = $346,319 )
2006	2006	UNIVERSITY OF ILLINOIS AT CHICAGO	809 S MARSHFIELD AVE, 511 MB	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	6	4/24/2006	COMPETING CONTINUATION	$346,319
														Subtotal = $346,319

Issue Date FY: 2005 ( Subtotal = $355,841 )
2005	2005	UNIVERSITY OF ILLINOIS AT CHICAGO	809 S MARSHFIELD AVE, 511 MB	CHICAGO	IL	60612	COOK	USA	Cancer Biology Research	000	5	1/28/2005	NON-COMPETING CONTINUATION	$355,841
														Subtotal = $355,841

Issue Date FY: 2004 ( Subtotal = $355,841 ) (Continued on the next page)
Grand Total All Awards = $8,925,030

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PI3K/PTEN/Akt signaling and the genesis of cancer

Award Number: R01CA090764

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2001

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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