Human cancer xenografts in immunocompromised mice provide an advanced genuine tumor model for research and drug development-A revisit of murine models for human cancers

Abstract

Molecular and cell biology studies have proven that human cancers are an enormously heterogenous disease, even if they originate from the same organ and tissue with identical morphological characteristics. Cancer cells in tumors from different individuals exhibit somewhat different characteristics on multiple levels, such as with respect to 1) their genetic polymorphism; 2) epigenetic mechanisms; 3) group gene activation/inactivation; 4) cell metabolism behavior; 5) aberrant incomplete terminal differentiation; 6) proliferative potential; and 7) hierarchical structure. These multiple parameters and their different combinations determine the biological characteristics of the cancer cells and their malignant/metastatic manifestations. With progress in medical research, numerous unique vulnerable targets of cancer cells have been identified from different tumors. Modern anti-cancer drug development focuses on target-based cancer cell inhibition and elimination have greatly improved the outcome of patients with some specific cancers. The murine model of human cancer has proven to be an essential procedure for the evaluation of drug efficacy in mammalian and a key link in transferring anti-cancer drug from laboratory to clinics. As classical murine cancer xenograft models with different human cancer cell lines display limited value for personalized precision medicine, creating a complete human xenograft cancer bank with all levels of abnormalities in mice has become desperately needed. This article is a review of the pros and cons of different human x murine cancer models and an attempt to find a more suitable model for the study and discovery of new anti-cancer drugs and different combination therapies in this small animal model.