Table 1.

SCFAs and cancer hallmarks

Cancer hallmark	Examples of therapeutic approaches	Examples of associated mutations	SCFA targets that block hallmarks*
Sustained proliferative signaling	EGFR inhibitors	Overexpression or mutation in ERBB genes; Wnt and Ras mutations	⇩ EGFR signaling by ⇩ Ras, myc, PI3K/Akt, c-Jun, STAT3; ⇧ PTEN, p53, p300-β-catenin
Evading growth suppressors	CDK inhibitors	Rb, p53, and CDKi mutations	⇧ p21WAF, p57; p53, PTEN; ⇩ c-myc
Avoiding immune destruction	Immunotherapy	Absence of neoantigens	⇩ PI3K/Akt, Stat3, NF-κB and HIF-1 depress PD-L1
Enabling replicative immortality	Telomerase inhibition	TERT promoter mutations	⇧ Differentiation; ⇩ telomerase activity
Tumor-promoting inflammation	Anti-inflammatory drugs	Ras pathway mutations	⇩ NF-κB, STAT3, gut dysbiosis, Th1 cytokines; ⇧ Th2 cytokines
Activating invasion and metastases	HGF/c-MET inhibitors	Mutations in the MET oncogene	⇧ Wnt, TIMPs, differentiation; ⇩ STAT3, MMPs, NF-κB, Ras, Hippo
Inducing angiogenesis	VEGF signaling inhibitors	Notch mutations	⇩ VEGF, Akt, Rho, STAT3, Ras, Hippo
Genome instability and mutations	PARP inhibitors	Mutations in DNA repair genes	⇩ Gut dysbiosis and ROS/RNS
Resisting cell death	Proapoptotic compounds	Wnt and Ras mutations	⇧ bax, FasL, p300-β-catenin; ⇩ bcl-2
Deregulating cellular energetics	Aerobic glycolysis inhibitors	Mutations in glycolytic enzyme encoding genes	⇧ PPARγ, HDACi, and HAT activity

^*Up and down arrows mean that SCFAs up- or down-regulate expression of the gene(s) encoding the protein(s) directly to the right of the arrow