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Sensitization of breast cancer and cancer stem cell to systemic therapy by Reishi

Award Number: SC3GM111171
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2021

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Sensitization of breast cancer and cancer stem cell to systemic therapy by Reishi - This proposal will investigate a therapeutic approach to sensitize breast cancer (BC) cells and cancer stem cells (CSCc) to therapy in one of the most lethal forms of breast cancer, which is inflammatory breast cancer (IBC). IBC is highly aggressive and chemo/radiation resistant cancer in which cells invade the vascular and lymphatic systems via generation of tumor emboli; a process regulated by protein synthesis. Accordingly, this study seeks to study the chemo/radiosensitizing role of Ganoderma lucidum (Reishi) via protein synthesis regulation. In IBC the eukaryotic initiation factor, eIF4GI is overexpressed. eIF4GI reprograms protein synthesis of select mRNAs to increase IBC invasion, resistance to therapy of the BC and CSC population through the DNA damage response pathway, and cancer cell survival. We published that Reishi reduces global protein synthesis, cap-dependent translation, the expression of eIF4GI in IBC cells and tumors, and Reishi also induces cancer cell death. However the role of Reishi on sensitizing cells to therapy via modulation of eIF4GI in advanced BC or CSC has not been studied. Therefore, we hypothesize that Reishi sensitizes IBC cells and tumors to conventional therapy through protein synthesis regulation via eIF4GI. Specific aim 1 will evaluate the effects of Reishi on newly translated mRNAs via polysome profile analysis coupled to microarrays. We will also study newly synthesized proteins as well as evaluate the activity of cap-independent translation upon Reishi treatment. Specific aim 2 will study the effect of eIF4GI silencing to understand if Reishi sensitizes BC or CSC to radiation or chemotherapy via the DDR pathway. Silenced and non-silenced BC cells treated with Reishi, radiation or carboplatin then sorted for CSC isolation via CD44+/Cd24- and ALDH markers. DDR pathway will be assessed via immunoblots in all cells. Specific aim 3 will assess sensitization in vivo. Sorted CSC from IBC and advanced BC will be injected into SHO-SCID mice. Reishi will be orally gavaged daily, then irradiated or subject to carboplatin chemotherapy. In vivo imaging will assess tumor volume and micrometastases will be evaluated 6-8 weeks post-treatments. These studies will investigate the role of a medicinal mushroom with potential to sensitize to therapy targeting the synthesis of key proteins that play a role in the pathology of this intractable disease.


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: 2023 ( Subtotal = -$3,994 )
2023	2019	UNIVERSIDAD CENTRAL DEL CARIBE, INC.	100 AVE LAUREL LOMAS VERDES	BAYAMON	PR	00956	BAYAMON	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	000	4	2/2/2023	SUPPLEMENT FOR EXPANSION	-$3,994
														Subtotal = -$3,994

Issue Date FY: 2022 ( Subtotal = -$4,743 )
2022	2017	UNIVERSIDAD CENTRAL DEL CARIBE, INC.	100 AVE LAUREL LOMAS VERDES	BAYAMON	PR	00956	BAYAMON	USA	Biomedical Research and Research Training	000	4	6/27/2022	NON-COMPETING CONTINUATION	-$4,743
														Subtotal = -$4,743

Issue Date FY: 2021 ( Subtotal = -$2,884 )
2021	2019	UNIVERSIDAD CENTRAL DEL CARIBE, INC.	100 AVE LAUREL LOMAS VERDES	BAYAMON	PR	00956	BAYAMON	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	002	4	9/5/2021	SUPPLEMENT FOR EXPANSION	-$339
2021	2017	UNIVERSIDAD CENTRAL DEL CARIBE INC	AVE LAUREL URB SANTA JUANITA	BAYAMON	PR	00956	BAYAMON	USA	Biomedical Research and Research Training	000	4	11/17/2020	NON-COMPETING CONTINUATION	$0
2021	2017	UNIVERSIDAD CENTRAL DEL CARIBE, INC.	100 AVE LAUREL LOMAS VERDES	BAYAMON	PR	00956	BAYAMON	USA	Biomedical Research and Research Training	001	4	9/5/2021	NON-COMPETING CONTINUATION	-$2,545
														Subtotal = -$2,884

Issue Date FY: 2019 ( Subtotal = $92,990 )
2019	2019	UNIVERSIDAD CENTRAL DEL CARIBE INC	AVE LAUREL URB SANTA JUANITA	BAYAMON	PR	00956	BAYAMON	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	001	4	4/29/2019	SUPPLEMENT FOR EXPANSION	$92,990
2019	2017	UNIVERSIDAD CENTRAL DEL CARIBE INC	AVE LAUREL URB SANTA JUANITA	BAYAMON	PR	00956	BAYAMON	USA	Biomedical Research and Research Training	000	4	4/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $92,990

Issue Date FY: 2017 ( Subtotal = $92,038 )
2017	2017	UNIVERSIDAD CENTRAL DEL CARIBE INC	AVE LAUREL URB SANTA JUANITA	BAYAMON	PR	00956	BAYAMON	USA	Biomedical Research and Research Training	000	4	8/18/2017	NON-COMPETING CONTINUATION	$92,038
														Subtotal = $92,038

Issue Date FY: 2016 ( Subtotal = $92,038 )
2016	2016	UNIVERSIDAD CENTRAL DEL CARIBE ESCUELA DE MED DE CAYEY	POST OFFICE BOX 60-327	BAYAMON	PR			USA	Biomedical Research and Research Training	000	3	8/9/2016	NON-COMPETING CONTINUATION	$92,038
														Subtotal = $92,038

Issue Date FY: 2015 ( Subtotal = $92,038 )
2015	2015	UNIVERSIDAD CENTRAL DEL CARIBE ESCUELA DE MED DE CAYEY	POST OFFICE BOX 60-327	BAYAMON	PR			USA	Biomedical Research and Research Training	000	2	8/4/2015	NON-COMPETING CONTINUATION	$92,038
														Subtotal = $92,038

Issue Date FY: 2014 ( Subtotal = $92,038 )
2014	2014	UNIVERSIDAD CENTRAL DEL CARIBE ESCUELA DE MED DE CAYEY	POST OFFICE BOX 60-327	BAYAMON	PR			USA	Biomedical Research and Research Training	000	1	8/28/2014	NEW	$92,038
														Subtotal = $92,038

Grand Total All Awards = $449,522

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Sensitization of breast cancer and cancer stem cell to systemic therapy by Reishi

Award Number: SC3GM111171

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2021

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