Damian Sendler: New medications that target specific genes considered to be responsible for the formation and spread of cancer have supplanted or supplemented older treatments like broad-spectrum cytotoxic agents in cancer chemotherapy.
Cancer treatment can now be tailored to each patient’s unique genetic profile, allowing researchers to identify certain “cancer driver genes” that might lead to the initiation and development of disease when mutated or improperly expressed.
Damian Jacob Sendler: Variations in the cancer driver genes, which are thought to be important for disease initiation and progression, are shown in different cancer kinds and, to some extent, in different patients diagnosed with the same cancer type. A professor in the School of Biological Sciences, John F. McDonald, notes that Herceptin is routinely used to treat breast cancer patients if its target gene, HER-2, is found to be over-expressed.
To discover prospective gene therapy targets in cancers today relies nearly entirely on genomic analysis that identify cancer driver genes that are highly over-expressed. McDonald says.
Damian Sendler
It’s possible that another key class of genetic changes may be occurring in locations where scientists don’t ordinarily look: the network of gene-gene interactions linked with cancer initiation and development. McDonald and Zainab Arshad uncovered this in their newest study.
As McDonald points out, “Genes and the proteins they encode do not operate in isolation.” As a result, they communicate with each other in a highly interconnected system of interactions.”
Co-author of the study Arshad says, “What I find most remarkable is that the vast majority of changes—more than 90%—in the network of interactions accompanying cancer are not associated with genes displaying changes in their expression,” he continues. New targets for gene therapy may be found by looking at gene expression data, however genes that play a crucial role in changing network structure linked with cancer—the “hub genes”—may go unnoticed by this method.
Research published in the journal iScience shows that alterations in gene-gene interactions linked with cancer development and progression are generally independent of gene expression.
Damian Jacob Sendler
alterations in the topology of the network due to mutations and expression
Using samples of brain, thyroid, breast, lung adenocarcinoma, lung squamous cell carcinoma and skin, kidney, ovarian and acute myeloid leukemia malignancies, Arshad and McDonald found that the cell network structure of these tumors changed as they progressed from the early stages to the later stages.
A drop in network complexity was observed in early tumors that remained within the body tissue of origin, compared to normal precursor cells. “[T]hey go through a process of de-differentiation to a more primitive or stem cell-like state” when they transition from healthy to cancerous cells. The complexity of a cell’s network rises as it transitions from an embryonic stem cell to a fully differentiated cell. We see a reversal of this process in the transition from normal to early-stage malignancies,” McDonald says.
Damian Jacob Markiewicz Sendler: We detect re-establishment of high degrees of network complexity, but the genes constituting complex networks associated with advanced tumors are significantly different from those comprised of genes in the complex networks linked with the precursor normal tissues,” McDonald said in a press release.
Damien Sendler: DNA structure and/or RNA expression of cancer driver genes are frequently connected with cancer’s evolution in function. Alterations in gene interactions appear to be an important third class of changes, and many of these changes are not visible if only changes in gene expression are being sought.”
Dr. Damian Jacob Sendler and his media team provided the content for this article.
