Intratumoral heterogeneity: Role of differentiation in a potentially lethal phenotype of testicular cancer
Shi-Ming Tu, Mehmet Asim Bilen, Kenneth R. Hess, Russell R. Broaddus, Scott Kopetz, Chongjuan Wei, Lance C. Pagliaro, Jose A. Karam, John F. Ward, Christopher G. Wood, Priya Rao, Zachary H. Tu, Rosale General, Adrienne H. Chen, Yago L. Nieto, Sai-ching J. Yeung, Sue-Hwa Lin, Christopher J. Logothetis and Louis L. Pisters
Article first published online: 28 MAR 2016 | DOI: 10.1002/cncr.29996
Whether intratumoral heterogeneity is derived from differentiation of aberrant progenitor cells or from mutation of driver genes is investigated in a relevant clinical model, and the results suggest that intratumoral heterogeneity is caused in part by differentiation of pluripotent progenitor cells. Integrated or multimodal therapy may be effective at addressing intratumoral heterogeneity and treating distinct tumor subtypes as well as potentially lethal tumor phenotypes; this finding has profound clinical implications regarding the origin of intratumoral heterogeneity and the implementation of precision medicine in testicular cancer and other solid tumors.