Table 2.

Pharmacometabolomic studies performed in BCa.

Cancer Therapy under Study	Samples	Instrumental and Statistical Analysis	Treatment Response	Metabolic Interpretation	Ref.
In vitro models
Chemotherapy: cisplatin (10 mM) 2 days of treatment exposure	Intracellular (lipophilic) metabolome of BCa cell lines: Cisplatin-sensitive cells T24S, n = 4 Cisplatin resistant cells T24R, n = 4	UPLC-MS PCA Student’s t-test p-value	Cisplatin resistance effects: ↑ CE (22:6); TG (49:1); TG (53:1)	Cisplatin-resistant condition altered lipid metabolism (storage of fatty acids and phospholipid biosynthesis)	[13]
Chemotherapy: cisplatin (10 μM) 12 h of treatment exposure	Intracellular (polar) metabolome of cell lines: Cisplatin-sensitive cells T24S, n ≥ 3 Cisplatin-resistant cells T24R, n ≥ 3	2D NMR (1H–13C HSQC) Student’s t test	Cisplatin resistance effects: ↑ acetate; fatty acids ↓ glucose; lactate; alanine:	Cisplatin-resistant condition was associated with an upregulation of glycolysis (Warburg effect) and fatty acid synthesis (cellular proliferation)	[92]
Human models
Chemotherapy: gemcitabine (50 mg, dissolved in 20 mL normal saline) 30 min of treatment exposure	Lipophilic tissue extracts: BCa untreated group, n = 12 BCa treated group, n = 12 adjacent normal group, n = 12 adjacent normal treated group, n = 12	LC-HRMS PCA Paired student t-test	Gemcitabine effects in BCa treated group: ↓ bilirubin; retinal Gemcitabine effects in adjacent normal treated group: ↑ histamine ↓ thiamine	-	[93]

2D NMR: two-dimensional nuclear magnetic resonance; ¹H–¹³C HSQC: ¹H–¹³C heteronuclear single quantum coherence; BCa: bladder cancer. CE: ceramides; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LC-HRMS: Liquid chromatography-high resolution mass spectrometry; LC-MS: liquid chromatography-mass spectrometry; PCA: principal component analysis; T24: human urinary bladder cancer patient cell line; TG: triglycerides; UPLC-MS: ultraperformance liquid chromatography-tandem mass spectrometry.