Table 1.

Literature overview of preclinical models for investigations of proton-specific research questions.

Model	RBE and LET	Normal Tissue Reaction	Molecular Responses	Tumor Biology	Combination Therapy	Personalized Medicine	Novel Radiation Treatment Modalities
2D cell culture	[20,37,83,90,91,92]	-	[20,21,24,75,76,77,78,79,80,81,82,93,94,95,96,97]	-	[99,100,101]	[104]	[36,78,84,85,86,87]
Spheroids, organoids	[38,40,111,138]	[38,143]	[38,133]	[135]	[40,133,136,137]	[38,111]	[72,139]
Other 3D models	[171]	[39]	-	[39]	-	-	[172]
Teleosts	[68,181]	[68,186]	-	[187,188,189]	-	[190,191]	[184]
Mice	[41,47,193,194,195,196,209,210,211,212]	[42,59,207,213,220,221,222]	[192,193]	[225,231,232]	[234]	-	[28,50,57,218,219,233,235]
Rats	[45,198,199,200,201,202,203]	[19,45,199,201,214,215,216,217,223,224]	-	-	-	[229]	[28,29,226,227,228]
Rabbits	-	[245,246]	-	[250,251,252,253,254,255]	-	-	-
Large mammals	-	[267,269,272,273]	-	[259]	-	-	[276]
In silico	[280,283,285,286,287,288,289,290,291,302,303,304,312,315,316,317,337,338]	[8,10,322,323,336,339,340]	[293,294,295,296,297,298,299]	[319,324]	[319]	[339]	-