Genetic Engineering & Biotechnology News

MAY15 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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28 | MAY 15, 2017 | | Genetic Engineering & Biotechnology News and resistance and recurrence monitoring. At Natera, we are launching a cfDNA prod- uct focused on early detection of recurrence. Mr. Kazinski Different analytes have differ- ent advantages with respect to the question a diagnostic test is meant to answer. cfDNA can be found and analyzed early and can, for this reason, be more efficient in some cases, such as the detection of residual disease or re- sistance development. CTCs for most cancers are detectable only at a more advanced stage of disease but allow for genomic, transcrip- tomic, and phenotypic characterization, pro- viding a more detailed insight into the dynam- ics and heterogeneity of the disease. Circulating RNA, either in CTCs or exo- somes, can help to correlate genomics and transcriptomic data, allowing for a better understanding of the disease mechanisms. Ms. Bramlett Molecular analysis from cell-free nucleic acid tends to be cheaper and faster than a similar analysis from circulating tumor cells. There is increasing use of RNA from cell-free material because together with cfDNA, they en- able expanded studies into rare variants, copy number, fusion gene detection, and expression. Cell-free nucleic acid has many of the same advantages as CTCs; the primary difference is whether protein markers or location informa- tion is important in the analysis. This suggests that there are situations where both cfDNA and CTC sources can be beneficial. For example, are copy number variations present in the same cell as a specific single nucleotide variant? Are cells displaying PDL-1 AB binding sites also harboring driver mutations? Answers to these questions could change therapy decisions in the future. GEN Should the goal of all liquid biopsies be to eventually become completely noninvasive? Are there substantial reasons to stick with blood as the medium of choice to isolate genetic material? Ms. Robinson Compared to acquiring a tu- mor biopsy sample, the current standard of care for cancer diagnosis, obtaining a blood sample for liquid biopsy, is relatively nonin- vasive. For the majority of cancers, it is hard to imagine another bodily fluid that is easier to collect and could replace blood for the purposes of liquid biopsy—and that could be used to collect intact tumor cells for down- stream molecular analysis. Dr. Patel It would depend on the cancer. For some cancers, completely noninvasive test- ing such as urine sampling is possible. But blood-based testing is an integral diagnos- tic modality for cancers such as lung and breast cancer. A blood draw is generally considered noninvasive or minimally invasive, and will most likely remain a major medium for isolating genetic material for the fore- seeable future. Dr. Ionescu-Zanetti We haven't found that obtaining blood samples is too invasive or challenging in most current settings, where the patient is already in the clinic and ob- taining blood is straightforward. A totally noninvasive sample format, urine for exam- ple, for early screening or frequent sampling post-surgery, could lead to an interesting consumer-driven self-sampling model, but we don't see that happening any time soon. Dr. Burke There are several mediums from which cells and DNA can be identified in- cluding urine. It really comes down to what is in the best interests of the patient—nonin- vasive and accurate testing is the way to go. Dr. Manaresi While noninvasively obtain- able body fluids, such as urine or sputum, hold the promise of complete noninvasive sampling, these are probably only suit- able for tumors in nearby tissues. Blood as source of tumor material has the potential to be applicable to a wide range of tumor types. Blood-based liquid biopsy can pro- vide complementary information to tradi- tional diagnostic tools in multiple settings, and when the pathological tissue is inacces- sible, it could be the only source of tumor information. Dr. Lin What ultimately matters is patient outcomes. If an invasive method improves survival more than a noninvasive approach, the collection method becomes less impor- tant. Similarly, if a noninvasive method per- forms better, whether due to ease of collec- tion or other unrelated factors, it should be adopted. We should all approach improve- ments with patient outcomes in mind. Mr. Kazinski For certain specific diseases, such as kidney or bladder cancers, urine may serve as a sufficient source of relevant markers in the future. However, blood will most likely be the primary source for isolat- ing and analyzing circulating biomarkers. The main reason is that blood allows not only the analysis of biomarkers of interest, but also the measurement of other clinically relevant parameters such as coinciding in- flammation. Ms. Bramlett There are currently several technologies that reduce risks while help- ing to build knowledge that leads to evalu- ation of the clinical utility of liquid biop- sies. Historically, we have obtained that information from solid tumor samples. Today, we talk about blood as a primary source of genetic material, but it's easy to think about other bodily fluids providing the same source material. These other sources raise additional questions beyond risk and invasiveness. The biology of a tumor is important—it affects the amount and quality of available source material. As such, we need to continue to develop flexible technologies that enable clinical researchers to investigate these op- tions more fully. Roundup Continued from page 27 Translational Medicine Insights Molecular Diagnostics Thermo Fisher Scientific will partner with SpeeDx to gain FDA clearance of the Australian developer's ResistancePlus™ MG molecular diagnostic for Mycoplasma genitalium, that is evolving into an antibiotic-resistant "superbug." The value of the partnership was not disclosed. Upon successful validation, SpeeDx will submit Resis- tancePlus MG to the FDA for use with the Applied Biosys- tems 7500 Fast Dx Real-Time PCR System, which offers 96-well, 5-color real-time PCR for in vitro diagnostic use. ResistancePlus MG is a multiplex qPCR test for detection of M. genitalium and five macrolide resis- tance markers from male and female urine and swab specimens. The test is designed to identify both M. genitalium and mutations in the 23S rRNA gene of the bacteria that have been shown to confer resistance to the antibiotic azithromycin. ResistancePlus MG is now marketed across Europe, Australia, and New Zealand, having received a CE mark and accreditation by the Australian Therapeutic Goods Administration. "With their reputation for scientific excellence, we are very pleased to partner with Thermo Fisher to bring this test to the U.S. market," SpeeDx CEO Colin Denver said in a statement. "Applied Biosystems qPCR instru- mentation has a long-standing reputation for quality and a wide install base across the region." Recent studies have shown a higher prevalence than gonorrhea for M. genitalium, which can cause symp- toms such as urethritis, cervicitis, endometritis, and pelvic inflammatory disease. SpeeDx also cited studies showing resistance has increased up to 40% in several countries to the macro- lide antibiotics, specifically azithromycin, that are the first-line treatment for M. genitalium sexually transmit- ted infections. Last year, the European Guideline on M. genitalium infections recommended complementing the molecu- lar detection of M. genitalium with an assay capable of detecting macrolide resistance-associated mutations. However, in the U.S., no FDA-cleared molecular diagnos- tic test exists for the detection of M. genitalium. n Thermo Fisher Partners with SpeeDx on FDA Clearance for 'Superbug' Diagnostic The use of circulating tumor DNA (ctDNA) as a liquid biopsy has potential utility in the clinical setting in monitoring tumor progression. Conventional biopsies are invasive and cannot be used when there is no visible tumor. ctDNA can be analyzed from collected blood and offers the ability to detect low levels of disease and more fully capture tumor heterogeneity. Anmery/Wikimedia Commons

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