Table 3.

Nonclinical data indicating that fasting increases the efficacy of chemotherapy.

Ref.	Materials	Mode of Fasting Plus CT	Outcome of Fasting Plus CT
[23]	Murine and human cancer cells	24 h Starvation before and 24 h Starvation during DXR or CP	More intense delay of progression of melanoma, glioma, and breast cancer cells compared to CT alone
	Subcutaneous allografts of murine breast cancer (4T1), melanoma (B16), glioma (GL26), metastatic neuroblastoma models (NXS2, Neuro-2a), and xenografts of human neuroblastoma (ACN), breast cancer (MDA-MB-231), and ovarian cancer (OVCAR3) cell lines	48 to 60 h fasting combined with DXR or CP
[130]	ZL55 mesothelioma cancer cells	CDDP with serum starvation	Sensitization of cancer cells, human mesothelioma xenografts, and human lung adenocarcinoma xenografts to CDDP via stimulation of ATM/Chk2/p53 signaling pathway
	Human ZL55 mesothelioma xenografts	48 h Fasting combined with CDDP
	Human lung carcinoma A549 xenografts
[137]	MCF7-xenograft-bearing 6–8-wk-old female NOD/SCIDγ mice	Cylic FMD plus TMX	Potentiation of FULV, TMX, palbociclib (or revertion of acquired resistance to FULV plus palbociclib via: ↓ insulin, ↓ IGF-1, ↓ leptin ↑PTEN ↓AKT ↑AMPK ↓mTOR ↓CCND1
	6-to-8-wk-old female BALB/c mice	Weekly 48 h fasting (n = 5) or FMD (n = 5) plus TMX
[141]	Balb/c mice orthotopically injected with a syngeneic triple negative breast cancer cell line (4T1)	30% CR combined with cisplatin/docetaxel	Reversal of chemotherapy-induced inflammation Downregulation of IGF-1R and insulin receptor signaling pathways Decrease lung metastatic burden
[142]	Primary mouse glia, murine GL26, rat C6 and human U251, LN229 and A172 glioma cells	STS combined with temozolomide	Sensitization of glioma cells, but not primary glia, to TMZ Sensitization of both subcutaneous and intracranial glioma models to chemotherapy
	Mice with subcutaneous or intracranial models of GL26 glioma	48 h Starvation prior to chemotherapy
[143]	CT26 colon carcinoma cell	48 h STS combined with OXP	Amplification of the toxicity and the DNA damage-dependent proapoptotic effect of OXP
	BALB/c mice models bearing subcutaneous CT26 colon cancer
[146]	Murine	FMD or STS combined with FMD with DXR or CP	Additive effect on tumor suppression via T cell-dependent killing of cancer cells
	Br east cancer (4T1)	FMD combined with DXR
	murine melanoma (B16) model
[148]	BxPC-3, MiaPaca-2, and Panc-1 cells	Culture in combination of gemcitabine and FMM	Reinforcement of the efficacy of gemcitabine via increasing levels of h ENT1, and reducing RRM1 levels
	Pancreatic cancer xenograft mice	24 h Starvation prior to gemcitabine
[149]	C57BL/6J mice bearing B16 melanoma tumors	48 h Fasting combined with DXR or CP	Efficacy of two fasting cycles in terms of inhibition of tumor growth equal to that of DXR or CP. Reinforcement of the efficacy of chemotherapy via induction of the proapoptotic effect of p53 due to disruption of REV1-p53 interaction

Abbreviations: CCND 1, cyclin D1; CDDP, cisplatin; Chk2, Checkpoint kinase 2; CP, cyclophosphamide; CT, chemotherapy; DXR, doxorubicin; FMM, fasting mimicking medium; FULV, fulvestrant; h ENT1, equilibrative nucleoside transporter; IGF-1R, insulin-like growth factor 1 receptor; OXP, Oxaliplatin; RRM1; ribonucleotide reductase M1; TMX, tamoxifen; TMZ, temozolomide; and wk, week.