In Nature Reviews Cancer, Dana-Farber Cancer Institute researchers Andriy Marusyk, Vanessa Almendro, and Kornelia Polyak discuss the intra-tumor heterogeneity of cancer and the implications of this diversity for the development of therapies and diagnostics. "It has become exceedingly apparent that the utility of profiles based on the analysis of tumors en masse is limited by intra-tumor genetic and epigenetic heterogeneity, as characteristics of the most abundant cell type might not necessarily predict the properties of mixed populations," the authors write. In addition to the malignant cells, the tumor's microenvironment is also an important factor to take into consideration. "Abnormal tumor microenvironments can result in increased genomic instability, further diversifying tumor cell populations," they add.
This heterogeneity needs to be acknowledged and accounted for during the analysis of a primary tumor, Marusyk, Almendro, and Polyak say. And the interactions between malignant and stromal cells within a tumor also need to be taken into account when an evaluation is performed and possible therapeutics developed. Further, they write, "it is worth interrogating whether intra-tumor phenotypic heterogeneity is linked to clinically important aspects of primary human cancers, such as subtype, prognosis, risk of metastases and therapeutic resistance." Given the importance of non-genetic factors that contribute to phenotypic heterogeneity, they add, "it may be worth exploring the link between non-genetic phenotypic diversity and clinical outcomes." Only by recognizing the importance of intra-tumor heterogeneity will researchers be able to develop effective combination therapies and technologies that will allow for the interrogation and understanding of tumors, the authors write.
(HT: Derek Lowe at In the Pipeline)