Abstract: Provided herein are methods and compositions of treating a condition by intratumorally administering MDM2 inhibitors. In some embodiments, the pharmaceutical compositions for intratumoral administration are formulated for controlled release and can comprise a biodegradable polymer.

Abstract: Provided herein are compositions and methods for studying cancer therapeutics and etiology, for example, mouse cancer models, cancer cell lines, and uses thereof. Human p53 knock-in (Hupki) mice with a Y220 (e.g., Y220C, Y220H, or Y220S) mutation in p53 are provided. These Hupki-Y220 mice can be used, for example, to examine tumorigenesis in different tissues, investigate mechanisms of gain of function, develop mouse models of cancer, generate cancer cell lines that can be implanted into recipient mice, and test potential therapeutics.

Abstract: A transgenic animal having a somatic cell in which at least one allele of an endogenous p53 and Pten gene is functionally disrupted is provided. The cell of the animal may be heterozygous or, more preferably, homozygous for the gene disruptions. The animals of the invention can be used to evaluate the efficacy of novel therapeutics and to identify novel points of therapeutic intervention for cancer. In certain embodiments, the transgenic animal is a transgenic mouse having functionally disrupted endogenous p53 and Pten genes. This mouse can be used to identify agents that inhibit the development of cancers, namely bladder cancers in humans in vivo.