Table 4.

The key findings from the studies on KDs and their role in overcoming therapeutic resistance in cancer

Study focus	Key findings	Mechanism/effect	Cancer type	References
KDs & Immune Checkpoint Blockade (ICB) Resistance	CKD and BHB delay tumor growth in ICB-resistant prostate cancer.	MHC-I upregulation, CD8 + T cell infiltration	Prostate Cancer	[139]
	HDAC inhibition and ketogenesis enhance ICB efficacy.	M1 macrophage polarization	Prostate Cancer	[139]
Keto-CARE Trial (Metastatic Breast Cancer)	WFKD reduces fasting glucose (16%), insulin (54%), and HOMA-IR (67%).	Improved insulin sensitivity	Metastatic Breast Cancer	[140]
	WFKD preserves lean body mass and reduces fat mass (45% to 37%).	Metabolic reprogramming	Metastatic Breast Cancer	[140]
KD + Melatonin in Breast Cancer	KD reduces ATP availability, impairing drug efflux pumps (P-glycoprotein).	Metabolic shift to ketolysis	Resistant Breast Cancer	[141]
	Melatonin enhances apoptosis (2.8-fold increase in caspase-3 activity).	Downregulation of resistance genes	Resistant Breast Cancer	[141]
	Combination therapy reduces tumor volume by 68% (cisplatin-resistant models).	Angiogenesis suppression (56% VEGF reduction)	Resistant Breast Cancer	[141]
KD in Liver Cancer	KD reduces tumor burden (65 mm³ vs. 420 mm³ in Western diet).	Reduced IL-6, cholesterol signaling	Liver Cancer	[142]
	KD increases pro-apoptotic markers (1.8-fold caspase-3, 2.1-fold p21).	Apoptotic regulation	Liver Cancer	[142]
KD + Metformin in Breast/Ovarian Cancer	Low glucose amplifies metformin’s cytotoxicity (ATP depletion).	Glycolytic suppression	Breast, Ovarian Cancer	[143]
	KD enhances metformin’s mTOR pathway inhibition.	OXPHOS inhibition	Breast Cancer	[143]