Table 1.

Summary of published examples of secondary adaptations that are associated with disease maintenance following downregulation of an initiating cancer stimulus

After downregulation/inactivation/antagonism of initiating stimulus
Initiating stimulus	disease maintenance after down-regulation of initiating stimulus	Accompany disease maintenance	Experimentally defined as disease-sustaining secondary adaptations	Disease regression factors	Experimental system	Tissue	References
SV40TAg	Low levels of pRb and Dp-1	Increased levels of Dp-1, Cdk4, Cdk6, cyclin D1, and phosphatase 2A; low p21 and p27	Increased levels of Cdk4		Genetically engineered mice	Submandibular salivary gland	37
Myc	Increased Erk1/2, Akt1, Stat3/5, p38 phosphorylation	Kras2 activating mutation	Kras2-activating mutation	p53, thrombospondin 1, CD4+ cells	Genetically engineered mice	Kras2 activating mutation: mammary tumors	54–56, 59–61
						Disease regression factors: hematopoietic tumors, T cell acute lymphoblastic leukemia
Wnt-1			Kras2-activating mutation		Genetically engineered mice	Mammary tumors	54
BCR-ABL				CD4+ cells	Genetically engineered mice	Pro-B cell leukemia	61
K-ras (G12D)	Increased Erk1/2, Akt1, Stat3/5, p38 phosphorylation				Genetically engineered mice	Lung and lymphatic tissue	56
ERα		Tamoxifen: increased Mucin4; increased MGMT; increased expression/ phosphorylation NF-κB pathway p50, RelB, and p65; decreased miR-375	Increased NF-κB pathway activity or decreased miR-375 following tamoxifen		Mucin4: MCF7/HER2–18 xenografts	Breast cancer	63–66, 76, 82
		Raloxifene: increased EGFR and Her2/Neu	Increased Her2/Neu following raloxifene		MGMT: breast cancer patients
		Estrogen deprivation: up-regulated PDGF/Abl pathway			NF-κB pathway, miR-375, EGFR/HER2
					PDGF/Abl:
					MCF7 cell variants