Table 1.

This table organizes the main experimental works in which a “tumor reversion process” has been observed or induced. Each work is presented highlighting the tumor model, the experimental methodology, the results and some relevant comments.

Tumor Model	Experimental Methodology	Results	Comments	Ref.
Ovarian teratocarcinoma	Clinical observation	Spontaneous regression, differentiation of cancer cells into normal tissue		Askanazy, 1907 [1]
Plant teratoma clonal cells	Succession of grafts on healthy tobacco plant	Disappearance of the teratoma and plant generation with seeds capable of giving life to a new plant	The results led the author to introduce the concept of pluripotentiality of cancer cells	Braun, 1959 [16]
Murine embryonic tumor cells	Transplantation on mice	Differentiation of cells	Hypothesis on the role of the tissue context in determining the fate of cancer cells	Pierce, 1961 [4]
Hamster sarcoma cells (induced by Rous sarcoma virus)	Succession of cell cultures and re-platings	Transformation of 19% of cells, which return to orienting themselves in an orderly manner, as in healthy tissues	The author uses the term “reversion” to describe results	Macpherson, 1965 [17]
Murine testicular teratocarcinoma cells (black mice)	Injection into murine blastocyst implanted in albino female mice	Development of healthy mice	One of the mice had black tufts, characteristic traits of the genome of teratocarcinoma cells	Brinster, 1974 [5]
Embryonic carcinoma cells from black mice	Blastocyst injection implanted in brown female mice	Normal fetal development; normal newborn mice feature hybrid traits between black and brown mice	Authors use the term “reversion” to describe their findings	Mintz and Illmensee, 1975 [6]
Lucke renal tumor cells (tumor of viral origin)	Planting on regenerative salamander limbs	Stopping of tumor growth and subsequent differentiation of cells	Failed to determine whether the differentiated cells came from cancer cells or healthy tissue	Rose and Wa llingford, 1948 [18,19]
Spontaneous tumors in animals	Observations on the rate of onset	Reduced occurrence of tumors in animals with high regenerative capacities		Gersch, 1951 [20]
Triton-induced epithelial tumors	Monitoring the spontaneous evolution of tumors	Tendency to tumor regression in anatomical areas with high regenerative potential	Results confirmed by histological analysis	Seilern-Aspangand Kratochwil, 1962 [21]
Liver cancer cells (marked with dye)	Injected into liver tissue	Reduction of malignancy and, in some cases, differentiation of cancer cells	Use of the term “partial reversion” to describe the phenotypic change of cells	Coleman, 1993 [22]
Neuroblastoma cells	Injected into 8 ½ day old murine blastocyst	Differentiation of tumor cells		Podesta, 1984 [23]
Leukemia cells	Injected into 10-day-old murine blastocyst	Correct hematopoietic maturation		Gootwine, 1982 [24]
Rous sarcoma virus	Injected into chicken embryos	No tumor development	If the virus is injected into adult chickens, then sarcoma develops	Dolberg and Bissell, 1984 [7]
Mouse melanoma cells	Implanted into embryos in murine uterus	Cell differentiation and normal embryonic development	Differentiation occurs when cells are implanted into a 14-day embryo	Gerschenson, 1986 [9]
Murine breast adenocarcinoma cells	Exposure to diffusible substances of murine embryonic mesenchyme	Differentiation of tumor cells		DeCosse, 1973 [25]
Primary murine lung cancer	Administration (in vivo) of homogenates of pregnant murine uteri	Suppression of tumor development		Biava, 1988 [26]
Glioblastoma, melanoma, renal adenocarcinoma, breast cancer, and lymphoblastic leukemia cells	Exposure to embryonic extracts of zebrafish taken before gastrulation	Reduction of cell proliferation rates		Biava, 2001; 2002 [27,28]
Human melanoma cells	Implanted in zebrafish embryos in the early stages of development	Suppression of malignant tumor phenotype and birth of healthy fish		Lee, Hendrix, 2005 [10]
Leukemia cells	Retinoic acid administration	Differentiation of leukemia cells into granulocytes, subsequently digested by macrophages	Today, acute promyelocytic leukemia is treated in most cases with differential treatments based on retinoic acid	Breitman, 1980 [29]
Various types of human tumors	Clinical remarks	Spontaneous regressions of tumors	Several cases of spontaneous regression of tumors have been analyzed, confirmed, and classified	Rohdenburg, 1918; Everson and Cole, 1966; Challis and Stam 1990; O’Regan and Hirshberg, 1993; Papac, 1998 [30,31,32,33,34]
Advanced hepatocarcinoma (179 cases)	In vivo administration of extracts of zebrafish embryos	20% of cancer regressions, of which 2.5% total stabilization progression in 16% of cases	Partial or complete disappearance of liver cancer in terminally ill patients	Livraghi, 2005 [35]
Melanoma cells and breast cancer cells	Exposed to embryonic stem cell factors	Reversal of the malignant phenotype and activation of apoptotic processes (nodal signal inhibition was also observed)	If cells are exposed to factors extracted from umbilical cord and bone marrow stem cells, then no phenotypic reversion is observed	Henrix, 2007; Postovit, 2008 [36,37]
Ovarian, prostate, and breast cancer cells	Microenvironmental exposure of human embryonic stem cells	Reversion of malignant phenotype block of cancer cells in phase G1	These results led researchers to hypothesize an inhibitory action on the cell cycle by factors extracted from embryonic stem cells	Giuffrida, 2009 [38]
Melanoma cells	Microenvironmental exposure of human embryonic stem cells	Reversion of malignant phenotype	The study identified some mRNAs involved in these cellular reprogramming processes.	Costa, 2009 [39]
Breast cancer cells	Exposure to salamander, frog, and mouse embryonic cell extracts	Stable reversal of malignant phenotype (confirmed with subsequent implantation of reprogrammed cells in immunosuppressed mice)	Re-expression of some cancer suppressor genes has been observed; mouse embryonic cells did not give results	Allegrucci, 2011 [40]
Breast cancer cells	Exposure to embryonic extracts of zebrafish taken at different times of embryogenesis	Reduction of invasiveness, migration, and proliferation parameters; action on cytoskeleton and TCTP downregulation	An activation method of reversion was identified, implying the down-regulation of TCTP by exposing the cells to a specific embryonic microenvironment composition that corresponds to a specific phase of embryogenesis	Proietti and Bizzarri, 2019 [12]