DETECTING CANCER IN A DROP OF BLOOD
Detecting and monitoring cancer is the mainstay of cancer care. To capture and contain the dreaded disease and mitigate its reach and power, studying and defining the cancer cell without resorting to organ biopsies using Circulating Tumor Cells (CTCs) is the new paradigm. The design of this (Liquid Biopsy) architecture was to fathom the following:
Estimate the Risk of Metastatic Relapse
Estimate the Risk of Progression
Real Time monitoring the efficacy of Therapy
Identifying Resistant mechanism
Identifying Molecular Targets
Estimating evolutionary changes in the cancer cell
Several mechanisms were developed and are currently being put through the paces; a) Liquid Biopsy Microchips, b) PCR assays using reverse transcription, c) Automated microscopy systems d) Multiplex approach to determine the Epithelial-Mesenchymal Transition, e) cell-free (cf)DNA assessment, f) Single Cell genomics with specific genetic mutations, g) Sequencing circulating (40-150 nanometer-sized membrane bound extracellular vesicles) exosomes, h) Using miRNA
The major problems that still exist are to be able to discern between the normal cell DNA and that of a malignant cell. Known mutations inherent to certain malignancies using micro-array chip technologies and other technological advances have overcome such restrictions to date and further analysis and experimentation will most certainly push the field into the clinical realm quickly. Dr. Geoffrey Oxnard of the Dana Farber Cancer Institute who did the (Liquid Biopsy) study "in 180 lung cancer patients," which showed their EGFR assay exhibited 100 percent positive predictive value for the detection of these mutations," they wrote in the Journal of the American Medical Association's JAMA Oncology. Wafik el-Deiry, MD recently said about the above study, "This study is not about the promise, it's about realizing the promise,"it's about realizing the promise."
Currently with the Immunotherapy challenges against malignancies, Adoptive therapies are being linked to mutation-specific CD4+T cells and using this technique is affording success in the Immunotherapy field.
Liquid Biopsy is on the horizon for pathologists and clinicians to change the way we detect, define, measure and ascertain the extent of the disease and evolutionary changes in cancer. Predictably this innovation will open the doors for a better understanding of cancer management and the one-size-fits-all method of cancer care will morph into true individualized patient care in the future.
One needs to imagine the future when a blood test will function as the pivotal point of patient care in cancer care and potentially in other chronic diseases as well. From detection to cure all through the eye of a molecular vision. Time will tell how this technology evolves and we as humans prosper from it.
Do you think that Liquid Biopsy will afford better Cancer management?
References:
Gerlinger M, Horswell S, Larkin J et al. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat Genet 2014; 46: 225–233.
Tran E, Turcotte S, Gros A et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 2014; 344: 641–645.
Taly V, Pekin D, Benhaim L et al. Multiplex picodroplet digital PCR to detect KRAS mutations in circulating DNA from the plasma of colorectal cancer patients. Clin Chem 2013; 59: 1722–1731.
Murtaza M, Dawson SJ, Tsui DW et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108–112.
Kahlert C, Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl) 2013; 91: 431–437.
E. Zandberga, V. Kozirovskis, A. Abols, D. Andrejeva, G. Purkalne, A. Line
Cell-free microRNAs as diagnostic, prognostic, and predictive biomarkers for lung cancer. Genes, Chromosomes Cancer, 52 (4) (2013 Apr), pp. 356–369
E. Sunami, A.T. Vu, S.L. Nguyen, A.E. Giuliano, D.S. Hoon
Quantification of LINE1 in circulating DNA as a molecular biomarker of breast cancer. Ann N Y Acad Sci, 1137 (2008 Aug), pp. 171–174
Estimate the Risk of Metastatic Relapse
Estimate the Risk of Progression
Real Time monitoring the efficacy of Therapy
Identifying Resistant mechanism
Identifying Molecular Targets
Estimating evolutionary changes in the cancer cell
Several mechanisms were developed and are currently being put through the paces; a) Liquid Biopsy Microchips, b) PCR assays using reverse transcription, c) Automated microscopy systems d) Multiplex approach to determine the Epithelial-Mesenchymal Transition, e) cell-free (cf)DNA assessment, f) Single Cell genomics with specific genetic mutations, g) Sequencing circulating (40-150 nanometer-sized membrane bound extracellular vesicles) exosomes, h) Using miRNA
The major problems that still exist are to be able to discern between the normal cell DNA and that of a malignant cell. Known mutations inherent to certain malignancies using micro-array chip technologies and other technological advances have overcome such restrictions to date and further analysis and experimentation will most certainly push the field into the clinical realm quickly. Dr. Geoffrey Oxnard of the Dana Farber Cancer Institute who did the (Liquid Biopsy) study "in 180 lung cancer patients," which showed their EGFR assay exhibited 100 percent positive predictive value for the detection of these mutations," they wrote in the Journal of the American Medical Association's JAMA Oncology. Wafik el-Deiry, MD recently said about the above study, "This study is not about the promise, it's about realizing the promise,"it's about realizing the promise."
Using some of these techniques researchers have been able to determine cell free and cell-bound DNA to contain targetable mutated genes and other amplified ones. For example determination of an emergence of EGFR amplification within lung caner, ERBB2 amplification in lung nodule (cancerous) BRCA2 mutation, KRAS mutation and others. Defining the genomic architecture of a heterogenous malignancy such as Clear Cell Carcinoma of the Kidney using driver prevalence through deep sequencing revealed evolutionary changes in the molecular determinants of the primary cancer. the deep multi- region sequencing is affording Precision Medicine a leg up in potentially improving cancer care for the individual. Diagnostic use of Liquid Biopsy is underway in various Trials across the world. Therapeutic modulations based on the diagnostics will certainly follow soon.
Currently with the Immunotherapy challenges against malignancies, Adoptive therapies are being linked to mutation-specific CD4+T cells and using this technique is affording success in the Immunotherapy field.
Liquid Biopsy is on the horizon for pathologists and clinicians to change the way we detect, define, measure and ascertain the extent of the disease and evolutionary changes in cancer. Predictably this innovation will open the doors for a better understanding of cancer management and the one-size-fits-all method of cancer care will morph into true individualized patient care in the future.
One needs to imagine the future when a blood test will function as the pivotal point of patient care in cancer care and potentially in other chronic diseases as well. From detection to cure all through the eye of a molecular vision. Time will tell how this technology evolves and we as humans prosper from it.
Do you think that Liquid Biopsy will afford better Cancer management?
References:
Gerlinger M, Horswell S, Larkin J et al. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat Genet 2014; 46: 225–233.
Tran E, Turcotte S, Gros A et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 2014; 344: 641–645.
Taly V, Pekin D, Benhaim L et al. Multiplex picodroplet digital PCR to detect KRAS mutations in circulating DNA from the plasma of colorectal cancer patients. Clin Chem 2013; 59: 1722–1731.
Murtaza M, Dawson SJ, Tsui DW et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013; 497: 108–112.
Kahlert C, Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl) 2013; 91: 431–437.
E. Zandberga, V. Kozirovskis, A. Abols, D. Andrejeva, G. Purkalne, A. Line
Cell-free microRNAs as diagnostic, prognostic, and predictive biomarkers for lung cancer. Genes, Chromosomes Cancer, 52 (4) (2013 Apr), pp. 356–369
E. Sunami, A.T. Vu, S.L. Nguyen, A.E. Giuliano, D.S. Hoon
Quantification of LINE1 in circulating DNA as a molecular biomarker of breast cancer. Ann N Y Acad Sci, 1137 (2008 Aug), pp. 171–174
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