Author Interviews, Biomarkers, Cancer Research / 20.08.2020 Interview with: Dr. Alexey Aleshin, M.D., MBA Senior Medical Director Natera What is the background for this study? Response: Checkpoint inhibitor-based immunotherapies (ICI)  have changed the management of a range of cancers of diverse histologies. While these therapies are well tolerated and efficacious, only a minority (<20%) of patients respond to treatment or derive durable clinical benefit from them, highlighting the need for a pan-cancer biomarker that can predict response prior to, or shortly after, treatment initiation. With immune checkpoint inhibitors (ICIs) rapidly becoming a cornerstone of cancer therapy, early determination of response to ICI treatment can optimize patient benefit and minimize the risk of toxicities, while potentially reducing unnecessary treatment and costs to patients and payers. Additionally, due to the nature of immune checkpoint inhibition, atypical patterns of response have emerged. For instance, tumor pseudoprogression — a transient increase in tumor size due to the infiltration of immune cells, followed by delayed shrinkage — has been reported in as much as 10% of patients receiving ICI therapy. Distinguishing pseudoprogression from true progression is clinically important to avoid premature discontinuation of a treatment that may have future benefit, or delay the initiation of an alternative line of therapy. However, they are hard to differentiate using current imaging techniques. Our study published in Nature Cancer earlier this month, demonstrates that bespoke circulating tumor DNA (ctDNA) testing may be a valuable tool that sheds light on both of these issues. (more…)
Author Interviews, Genetic Research, Nature, NYU / 17.08.2020 Interview with: Professor Aneel K Aggarwal, PhD Pharmacological Sciences and Oncological Sciences Icahn School of Medicine at Mount Sinai What is the background for this study? Response: DNA polymerase ζ  (Pol ζ) is the crucial enzyme that allows cells to cope with DNA damage resulting from exposure to environmental and industrial carcinogens and to other daily genotoxic stresses. At the same time, Pol ζ has emerged as an important target for discovery of therapeutics in the treatment of chemotherapy-resistant cancers. What are the main findings?   Response: We have succeeded in resolving the 3-D atomic structure of the complete Pol ζ enzyme using cryo-electron microscopy. (more…)
Author Interviews, Cancer Research, Genetic Research, Pharmaceutical Companies / 23.10.2019 Interview with: Ambry GeneticsRachid Karam, MD, PhD Ambry Genetics Aliso Viejo, California What is the background for this study? Response: DNA genetic testing is a powerful tool used to tailor medical care based on an individual’s cancer risk. However, even medical grade DNA genetic testing can produce inconclusive results, finding a change in our DNA to be a variant of unknown significance (a VUS) and failing to determine whether it increases cancer risk. When this happens, healthcare providers might not have the information needed to recommend appropriate preventive and early detection steps, or certain cancer treatments, and relatives may not be referred for genetic testing for their own care. In this study, investigators from Ambry, Dana-Farber Cancer Institute, Cedars-Sinai Medical Center, Rutgers Cancer Institute, and University of Kansas Cancer Center demonstrated that performing both DNA and RNA genetic testing reduces inconclusive results enabling clinicians to offer cancer screening and treatment resources to the right patients. (more…)
Author Interviews, Cancer Research, Genetic Research / 08.04.2019 Interview with: Eunhee Yi, Ph.D. Postdoctoral Associate The Jackson Laboratory What is the background for this study? What are the main findings?  Response: Recurrence after therapy for glioblastoma (GBM) is unavoidable. There are substantial differences among the cells of GBM tumors in the abundance and types of genetic materials. This heterogeneity is a major driver of therapy failure and disease progression. We previously reported that extrachromosomal DNA (ecDNA) elements, which reside outside the linear genome and represent a mechanism to amplify and activate oncogenes, is a potential cause of the increasing genetic diversity in GBM. Our current study is focused on the development of a novel cytogenetic tool to visualize ecDNA to visualize the behavior of these elements in live cells. We have leveraged the unique properties of ecDNA to develop a CRISPR-based “ecDNA tracing toolbox (EDTB)”.  (more…)
Aging, Author Interviews, Genetic Research / 23.09.2016

Dr-Bastiaan-Heijmans.jpg Interview with: Dr. Bastiaan Heijmans Leiden University Medical Center What is the background for this study? What are the main findings? Response: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. In a large-scale analysis of the methylome of over 3000 individuals, we discovered and validated 6000 sites in the genome that became more variable in their DNA methylation level with age. These sites frequently co-localized with repressed regions that are characterized by polycomb repression. While sites accumulating variability with age were commonly associated with the expression of (neuro)developmental genes in cis, they were linked to transcriptional activity of genes in trans that have a key role in well-established ageing pathways such as intracellular metabolism, apoptosis, and DNA damage response. (more…)
Author Interviews, Case Western, Genetic Research / 22.09.2016 Interview with: Carlos E. Crespo-Hernández PhD Associate Professor and Co-director of the Center for Chemical Dynamics Department of Chemistry Case Western Reserve University Cleveland, Ohio What is the background for this study? What are the main findings? Response: Two new letters of DNA have recently been successfully incorporated and replicated by a modified strain of E. coli, thus generating the world’s first semi-synthetic organism with an expanded genetic alphabet. With the expansion of the genetic alphabet, the question arises as to whether the incorporation of unnatural DNA base pairs into cells can adversely affect the integrity of the genetic code and the viability of the cells upon exposure to sunlight or even conventional laboratory lighting. Natural DNA is susceptible to damage by ultraviolet light, but this damage is largely repaired by enzymatic repair mechanisms in living cells. Our recent study has found that the two new, unnatural DNA bases—d5SICS and dNaM—are able to efficiently absorb near-visible light, which is abundant in sunlight and standard fluorescent lighting. Not only that, but upon absorbing near-visible light these unnatural bases produce up to 100 times more reactive species than the most reactive natural DNA base. A line of skin cancer cells incorporating one of these unnatural DNA bases was used to investigate these effects on living cells. Following exposure to a low dose of near-visible light, we observed an increase in the generation of reactive oxygen species within cells containing the unnatural DNA base and a significant decrease in cell survival. (more…)