MOLECULAR DIAGNOSTICS :: TUMOR MARKERS


What’s next in Cancer Biomarker Development? The National Cancer Institute (NCI) is spearheading several key initiatives to address the slow progress in early cancer biomarker development.12


This strategic approach will spur new research


and evaluation of new diagnostics and therapeutics. NCI’s Early Detection Research Network (EDRN), a collab-


orative consortium of academic and private-sector investiga- tors, has focused on the systematic discovery, development, and validation of biomarkers and imaging methods to detect early-stage cancers and to assess risk for developing cancer. The goal of EDRN is to develop biomarkers that can distinguish aggressive early-stage cancers from slow-growing cancers that would never cause symptoms to reduce overtreatment. Cancer researchers are turning to proteomics (the study of protein structure, function, and patterns of expression) and proteogenomics (the integration of proteomics with genomics and gene expression analysis, or transcriptomics, which involves the study of all RNA molecules in a cell.) with the hope of developing novel biomarkers that can be used to identify cancer in its early stages, to predict the effectiveness of treatment, and to predict the chance of cancer recurrence. NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC)


is using a proteogenomic approach for tumor marker discovery for a growing number of cancers, including colorectal, breast, and ovarian cancers. By systematically identifying proteins (and associated biological processes) that originate from alterations in cancer genomes, CPTAC researchers have discovered new tumor subtypes, tumor microenvironment variations, and new potential proteins for targeted drug therapy. Recent innovations have suggested that these analyses could be done on a microscale using very small amounts of tumor tissue obtain from a biopsy. NCI’s Molecular Applications for Therapy Choice (NCI-


MATCH) and NCI-COG Pediatric MATCH clinical trials are using a precision medicine approach to assign patients to treat- ment by gene mutations in their tumors rather than by the type of cancer they have. By analyzing the response of patients to these targeted agents, and the underlying genomic alterations associated with these responses, researchers are identifying potentially new molecular targets for cancer therapy. Companion studies associated with these trials will also allow researchers to identify new biomarkers for determining response to therapies and for predicting treatment resistance. The NCI Cancer Moonshot Biobank is working with patient participants at community hospitals around the country to encourage them to donate tissue and blood specimens over the course of their cancer treatment. The specimens are sent to researchers who use them to better understand cancer and potentially identify tumor markers.


Summary The limited delivery of breakthroughs in early cancer biomark- ers has been frustrating, but there is hope that new strategic investments by NCI, academics and diagnostic companies will be the stimulus for new diagnostic tools. The intersection of large datasets and artificial intelligence may provide clues to new approaches of evaluating risks (and targeting diagnostics to high-risk individuals), utilizing the best tests we have today while looking forward to new and better tests being developed. In the interim, we need to encourage people to be screened with cancer biomarkers that have been proven to be effective such as for cervical cancer, colorectal cancer, and, when indicated with appropriate consultation, prostate cancer. Increased adherence to guidelines will have dramatic impacts in driving down cancer prevalence and mortality. Furthermore,


the COVID-19 pandemic has left a gap of people who have skipped or delayed routine healthcare services, including cancer screening.13


We must be proactive in safely closing the gap in


care with biomarker-based screening, in most cases, having the fewest barriers for large scale implementation. Although current testing has challenges and nuances as discussed, it offers the ability to screen large numbers of patients who may have delays in care, which, if not addressed, have the potential to increase cancer related morality.


REFERENCES:


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2. Brawley OW. Trends in prostate cancer in the United States. J Natl Cancer Inst Monogr. 2012;2012(45):152-156. doi:10.1093/jncimonographs/lgs035.


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4. Springer SU, Chen CH, Rodriguez Pena MDC, et al. Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy. Elife. 2018;7:e32143 doi: 10.7554/eLife.32143.


5. Wang Y, Li L, Douville C, et al. Evaluation of liquid from the Papanico- laou test and other liquid biopsies for the detection of endometrial and ovarian cancers. Sci Transl Med. 2018; 10(433):eaap8793. doi: 10.1126/ scitranslmed.aap8793.


6. Lennon AM, Buchanan AH, Kinde I, et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. 2020; 369(6499):eabb9601. doi: 10.1126/science.abb9601.


7. Duffy MJ. Clinical uses of tumor markers: a critical review. Crit Rev Clin Lab Sci. 2001:38(3):225-262, doi: 10.1080/20014091084218.


8. Buys SS, Partridge E, Black A, et al. Effect of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295–2303. doi:10.1001/jama.2011.766.


9. Rodriguez-Homs, M, Baack Kukreja, J. Bladder cancer biomarkers: Past and future directions. BJUI Compass. 2021; 2: 7– 8. doi.org/10.1002/bco2.61


10. Bangma CH, Loeb S, Busstra M, et al. Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers. Eur Urol. 2013;64(1):41-7. doi: 10.1016/j.eururo.2013.02.036.


11. Schlomer BJ, Ho R, Sagalowsky A, et al. Prospective validation of the clinical usefulness of reflex FISH assay in patients with atypical cytology for the detection of urothelial carcinoma of the bladder. J Urol. 2010; 183(1):62-7. doi: 10.1016/j.juro.2009.08.157.


12. Cancer Biomarkers | Division of Cancer Prevention, EDRN — Early Detection Research Network (nih.gov), CPTAC | Office of Cancer Clini- cal Proteomics Research, NCI-MATCH Precision Medicine Clinical Trial - National Cancer Institute, and Cancer Moonshot — National Cancer Institute Accessed October 15, 2021.


13. Kaufman HW, Chen Z, Niles JK, Fesko YA. Changes in Newly Identified Cancer Among US Patients From Before COVID-19 Through the First Full Year of the Pandemic. JAMA Netw Open. 2021;4(8):e2125681. doi:10.1001/ jamanetworkopen.2021.25681.


Yuri A. Fesko, MD, a board-certified oncologist, is Executive Medical Director of Medical Affairs at Quest Diagnostics.


Harvey W. Kaufman, MD, a board-certified pathologist, is Senior Medical Director at Quest Diagnostics. A 29-year veteran of Quest Diagnostics, Kaufman was an original and still active member of the Laboratory Working Group of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (formerly the National Kidney Disease Education Program).


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