Granted Patent
B2
US 12,306,174 · App. 17/273,294 · Granted May 20, 2025
Diagnosis of cancer
Inventors:
Max Allsworth (Cambridge, GB); Edoardo Gaude (Cambridge, GB); Marc van der Schee (Cambridge, GB)
Assignee:
Owlstone Medical Limited
View Patent ↗
Loading inventors, assignments & file history…
Abstract
A method for the early detection and monitoring of the progression of cancer by detecting breath biomarkers is provided. The method comprises assessing the activity of an aldo-keto reductase by measuring the concentration of an exogenous substrate for said enzyme and/or measuring the concentration of a metabolite of said substrate in exhaled breath of a subject. Preferably, the cancer is lung cancer.
Claims (22)
1. A method for the detection or prognosis of cancer comprising assessing the activity of an aldo-keto reductase (AKR) by measuring the concentration of an exogenous substrate for said AKR and/or measuring the concentration of a metabolite of said substrate in exhaled breath of a subject, wherein the cancer is lung cancer and where in said AKR is AKR1B10 or AKR1B15.
2. The method according to claim 1 wherein the substrate and/or its metabolite is a volatile organic compound (VOC).
3. The method according to claim 1 wherein the substrate is a generally recognized as safe (GRAS) compound.
4. The method according to claim 1 wherein the substrate is labelled.
5. The method according to claim 1 wherein said lung cancer is selected from small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma or adenocarcinoma.
6. The method according to claim 1 wherein the substrate is labelled retinaldehyde.
7. The method according to claim 6 wherein said label is 12C, 13C, 14C, 2H, 14N or 18O.
8. The method according to claim 1 wherein said substrate is cinnamaldehyde, citral or pyridine-3-aldehyde.
9. The method according to claim 1 wherein said method comprises establishing a test subject value based on a concentration of said substrate or metabolite.
10. The method according to claim 9 wherein said test subject value is compared to one or more reference value and wherein a difference in the test subject value and a reference value indicates a likelihood of cancer.
11. The method according to claim 10 wherein said reference value is the value of a subject that has been diagnosed with a cancer.
12. The method according to claim 11 wherein said reference value is the value of a subject who has not been diagnosed with cancer.
13. The method according to claim 1 wherein the concentration of more than one exogenous substrates and/or the concentration of more than one metabolites is measured.
14. The method according to claim 1 wherein the method comprises providing the substrate to the subject.
15. The method according to claim 1 wherein the method comprises collection of a breath sample from said subject.
16. The method according to claim 1 wherein the substrate is not labelled.
17. A method for monitoring the progression of cancer in a subject diagnosed with cancer comprising assessing the activity of an aldo-keto reductase (AKR) by measuring the concentration of an exogenous substrate for said AKR and/or measuring the concentration of a metabolite of said substrate in exhaled breath of the subject, wherein the cancer is lung cancer and wherein said AKR is AKR1B10 or AKR1B15.
18. The method according to claim 17 wherein the subject has undergone anti-cancer treatment.
19. A method for determining efficacy of a treatment comprising in a subject diagnosed with cancer assessing the activity of an aldo-keto reductase (AKR) by measuring the concentration of an exogenous substrate for said AKR and/or measuring the concentration of a metabolite of said substrate in exhaled breath of the subject wherein said subject has received anti-cancer treatment, wherein the cancer is lung cancer and wherein said AKR is AKR1B10 or AKR1B15.
20. A method of treating cancer in a subject comprising assessing the activity of an aldo-keto reductase (AKR) by measuring the concentration of an exogenous substrate for said AKR and/or measuring the concentration of a metabolite of said substrate in exhaled breath of the subject wherein said subject has received anti-cancer treatment, wherein the cancer is lung cancer and wherein said AKR is AKR1B10 or AKR1B15.
21. A system for the detection of cancer comprising assessing the activity of an aldo-keto reductase (AKR) by measuring the concentration of an exogenous substrate for said AKR and/or measuring the concentration of a metabolite of said substrate in exhaled breath of a subject wherein said system comprises a device for capturing a breath sample from the subject, wherein the cancer is lung cancer and wherein said AKR is AKR1B10 or AKR1B15.
22. A kit comprising a system according to claim 21 .
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 29, 2021
From: ALLSWORTH, MAX; GAUDE, EDOARDO; VAN DER SCHEE, MARC
To: OWLSTONE MEDICAL LIMITED
Reel/Frame 056088/0919 →
Priority Claims (1)
GB 1814350
· Sep 4, 2018
· national
Continuity (1)
References Cited (129)
US 5818580A
· Murnick
· 1998
[cited by examiner]
US 20050233459A1
· Melker et al.
· 2005
[cited by applicant]
US 20070172424A1
· Roser
· 2007
[cited by applicant]
US 20090005270A1
· Melker et al.
· 2009
[cited by applicant]
US 20100255598A1
· Melker et al.
· 2010
[cited by applicant]
US 20120115177A1
· Rodenrys
· 2012
[cited by applicant]
US 20120183949A1
· Hyde
· 2012
[cited by examiner]
US 20160101194A1
· Dennis
· 2016
[cited by applicant]
US 20220228192A1
· Gaude et al.
· 2022
[cited by applicant]
CN 2003215123A
· 2003
[cited by applicant]
CN 104650234A
· 2015
[cited by applicant]
CN 105403615A
· 2016
[cited by applicant]
JP 3790792B2
· 2006
[cited by examiner]
JP 2008513026A
· 2008
[cited by applicant]
WO 2006034370A2
· 2006
[cited by applicant]
WO 2007103474A1
· 2007
[cited by applicant]
WO 2008134026A1
· 2008
[cited by applicant]
WO 2012140660A1
· 2012
[cited by applicant]
WO 2013040494A1
· 2013
[cited by applicant]
WO 2015064063A1
· 2015
[cited by applicant]
WO 2017187120A1
· 2017
[cited by applicant]
WO 2017187141A1
· 2017
[cited by applicant]
WO 2018009939A1
· 2018
[cited by applicant]
WO 2018009939A9
· 2018
[cited by applicant]
WO 2018211280A1
· 2018
[cited by applicant]
WO WO2019220145A1
· 2019
[cited by applicant]
WO 2020049300A1
· 2020
[cited by applicant]
Machado et. al. Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med. Jun. 1, 2005;171(11):1286-91. doi: 10.1164/rccm.200409-1184OC. (Year: 2005).
[cited by examiner]
Machine Translation of JP3790792B2 (Year: 2003).
[cited by examiner]
In vitro analysis of volatile organic compounds in search of potential biomarkers of lung cancer; Kamila Schmidt, University of Salford Manchester, Aug. 2016 (Year: 2016).
[cited by examiner]
Nishinaka et al., “Identification and characterization of functional antioxidant response elements in the promoter of the aldo-keto reductase AKR1B10 gene”, Chemico-Biological Interactions 276, 160-166 (2017).
[cited by applicant]
Qiongfang, C., et al., “Expression and clinical significance of aldo-ketone reduction family 1B10 protein in non-small cell lung cancer” Theory and Practice of Diagnostics, vol. 11, No. 2, 2012, pp. 167-171.
[cited by applicant]
Penning, T. M., et al., “AKR1B10: A New Diagnostic Marker of Non-Small Cell Lung Carcinoma in Smokers”, Clin Cancer Res, vol. 11, No. 5, 2005, pp. 1687-1690.
[cited by applicant]
International Preliminary Report on Patentability for International Application No. PCT/GB2019/051381, entitled Method to Evaluate Metabolic Activity of Liver Enzymes, consisting of 10 pages. Date Mailed: Nov. 17, 2020.
[cited by applicant]
Alvarez, S.W. et al., “NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis,” Nature, 551(7682): 639-643 (Nov. 2017).
[cited by applicant]
Ayala, A. et al., “Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal,” Oxidative Medicine and Cellular Longevity, vol. 2014, Article ID 360438, Published May…
[cited by applicant]
Bachur, N. 1976. “Cytoplasmic Aldo-Keto Reductases: A Class of Drug Metabolizing Enzymes.” Science, 193 (4253): 595-597.
[cited by applicant]
Barski, O.A. et al., “The Aldo-Keto Reductase Superfamily and Its Role in Drug Metabolism and Detoxification,” Drug Metabolism Reviews, 40 (4): 553-624 (2008).
[cited by applicant]
Blaser, M.J., Disappearing microbiota and epidemic obesity, Depts. of Medicine and Microbiology, New York University School of Medicine, Langone Medical Center, Dept. of Biology, NYU, 22 pages (2007).
[cited by applicant]
Cao, D. et al., “Identification and Characterization of a Novel Human Aldose Reductase-like Gene,” The Journal of Biological Chemistry, 273(19): 11429-11435 (1998).
[cited by applicant]
Ciccarelli, F.D. et al., “Toward Automatic Reconstruction of a Highly Resolved Tree of Life,” Science, 311: 1283-1287 (2006).
[cited by applicant]
Costea, P.I. et al., “Towards standards for human fecal sample processing in metagenomic studies,” Nature Biotechnology, 35: 1069-1076 (2017).
[cited by applicant]
DeNicola, G.M. et al., “Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis,” Nature, 475(7354): 106-109 (2012).
[cited by applicant]
Dixon, S.J. et al., “Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis,” eLife 3, 25 pages (2014).
[cited by applicant]
Fan, T.WM. et al., “Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metaolomics (SIRM),” Molecular Cancer, 8: 41, 19 pages (2009).
[cited by applicant]
Faubert, B. et al., “Lactate metabolism in human lung tumors,” Cell, 171(2): 358-371 (2017).
[cited by applicant]
Fukumoto, S. et al., “Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non-Small Cell Lung Carcinomas,” Clinical Cancer Research, 11: 1776-1785 (2005).
[cited by applicant]
Gaude, E. and C. Frezza, “Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival,” Nature Communications, 7, Article No. 13041, 9 pages (2016).
[cited by applicant]
Giménez-Dejoz, J. et al., “Substrate Specificity, Inhibitor Selectivity and Structure-Function Relationships of Aldo-Keto Reductase 1B15: A Novel Human Retinaldehyde Reductase,” Edited by Fernando Rodrigues-Lima, PLOS O…
[cited by applicant]
Grimshaw, C.E., “Aldose Reductase: Model for a New Paradigm of Enzymic Perfection in Detoxification Catalysts,” Biochemistry, 31(42): 1 page (1992).
[cited by applicant]
Hensley, C.T. et al., “Metabolic heterogeneity in human lung tumors,” Cell, 164(4): 681-694 (Feb. 2016).
[cited by applicant]
Jin, J. et al., “Aldo-keto Reductase Family 1 Member B10 Mediates Liver Cancer Cell Proliferation through Sphingosine-1-Phosphate,” Scientific Report, 6: 22746, 11 pages (2016).
[cited by applicant]
Li, S.S. et al., “Durable coexistence of donor and recipient strains after fecal microbiota transplantation,” Science, 352(6285): 5 pages (2016).
[cited by applicant]
MacLeod, A.K. et al., “Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer,” British Journal of Cancer, 115: 1530-1539 (2016).
[cited by applicant]
Martin, Hans-Jörg and E. Maser, “Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes,” Chemico-Biological Interactions, 178: 145-150 (2009).
[cited by applicant]
Mende, D.R. et al., “Accurate and universal delineation of prokaryotic species,” Nature Methods, 8 pages (2013).
[cited by applicant]
Mochalski, P. et al., “Release and uptake of volatile organic compounds by human hepatocellular carcinoma cells (HepG2) in vitro,” Cancer Cell International, 13:72, 9 pages (2013).
[cited by applicant]
Green et al., Molecular Cloning, A Laboratory Manual, Fourth Edition, vol. 1, Cold Spring Harbor Laboratory Press, 34 pages (2012).
[cited by applicant]
Pavlova, N.N. and C.B. Thompson, “The Emerging Hallmarks of Cancer Metabolism,” Cell Metabolism, 23(1): 27-47 (2016).
[cited by applicant]
Petrash, J.M. et al., “Involvement of Cysteine Residues in Catalysis and Inhibition of Human Aldose Reductase,” The Journal of Biological Chemistry, 267(34): 24833-24840 (1992).
[cited by applicant]
Quince, C. et al., “Shotgun metagenomics, from sampling to sequencing and analysis,” Nature Biotechnology, 35: 833-844 (2017).
[cited by applicant]
Reznik, E. et al., “Mitochondrial DNA copy number variation across human cancers,” eLIFE 5, 20 pages (2016).
[cited by applicant]
Ross, B.M. et al., “The Use of SIFT-MS to Investigate Headspace Aldehydes as Markers of Lipid Peroxidation,” Current Analytical Chemistry, 9: 600-613 (2013).
[cited by applicant]
Schallschmidt, K. et al., “Investigation of cell culture volatilomes using solid phase micro extraction: Options and pitfalls exemplified with adenocarcinoma cell lines,” Journal of Chromatography B, 1006: 158-166 (2015…
[cited by applicant]
Sellers, K. et al., “Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation,” The Journal of Clinical Investigation, 125(2): 687-698 (2015).
[cited by applicant]
Singh, A. et al., “Dysfunctional KEAP1-NRF2 Interaction in Non-Small-Cell Lung Cancer,” PLOS Medicine, vol. 3, Issue 10, 1865-1876 (2006).
[cited by applicant]
Sorek, R. et al., “Genome-wide experimental determination of barriers to horizontal gene transfer,” Science, vol. 318, Issue 5855, pp. 1449-1452 (2007).
[cited by applicant]
Srivastava, S. et al., “Aldose Reductase-catalyzed Reduction of Aldehyde Phospholipids,” J Biol Chem, 279(15): 53395-53406 (2004).
[cited by applicant]
Stockwell, B.R. et al., “Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease,” Cell, 171(2): 273-285 (2017).
[cited by applicant]
Tong, Y-H et al., “Keap1-Nrf2 pathway: A promising target towards lung cancer prevention and therapeutics,” Chronic Diseases and Translational Medicine 1: 175-186 (2015).
[cited by applicant]
Yan, R. et al., “Aldo-keto reductase family 1 B10 gene silencing results in growth inhibition of colorectal cancer cells: Implication for cancer intervention,” Int. J. Cancer, 121: 2301-2306 (2007).
[cited by applicant]
Yarza, P. et al., “Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences,” Nature Reviews, 12: 635-645 (2014).
[cited by applicant]
Yin, H. et al., “Free Radical Lipid Peroxidation: Mechanisms and Analysis,” Chemical Reviews, 111: 5944-5972 (2011).
[cited by applicant]
Yoshitake, H. et al., “Aldo-keto reductase family 1, member B10 in uterine carcinomas: a potential risk factor of recurrence after surgical therapy in cervical cancer,” Int J Gynecol Cancer, 17: 1300-1306 (2007).
[cited by applicant]
Zhao, D. et al., “Combinatorial CRISPR-Cas9 metabolic screens reveal critical redox control points dependent on the KEAP1-NRF2 regulatory axis,” Mol Cell, 69(4): 699-708 (2018).
[cited by applicant]
Zhou, Z. et al., “Inhibiting proliferation and migration of lung cancer using small interfering RNA targeting on Aldo-keto reductase family 1 member B10,” Molecular Medicine Reports, 17: 2153-2160 (2018).
[cited by applicant]
Applicant: Owlstone Med Ltd, Diagnosis of Cancer, Examination Report mailed Jul. 24, 2023 for EP Application No. 19766318 filed Sep. 4, 2019, 12 pages.
[cited by applicant]
Zhou Y, et al., Expression of AKRs superfamily and prognostic in human gastric cancer, Feb. 22, 2023, 33041, 102(8), Jul. 13, 2023.
[cited by applicant]
Amann et al., “Analysis of Exhaled Breath for Disease Detection”, Annual Review of Analytical Chemistry, vol. 7, 2014, pp. 455-482.
[cited by applicant]
Amann et al., “Analysis of Exhaled Breath for Screening of Lung Cancer Patients”, Magazine of European Medical Oncology, vol. 3, No. 3, Oct. 1, 2010, pp. 106-112.
[cited by applicant]
DeLano et al. “Volatile Decay Products in Breath During Peritonitis Shock are Attenuated by Enteral Blockade of Pancreatic Digestive Proteases”, Shock, vol. 48, No. 5, 2017, pp. 571-575.
[cited by applicant]
Gaude et al., “Targeted breath analysis: exogenous volatile organic compounds (EVOC) as metabolic pathway-specific probes,” Journal of Breath Research, vol. 13, No. 3, May 17, 2019, 13 pages.
[cited by applicant]
Modak et al., “A Rapid Non Invasive L-DOPA-13C Breath Test for Optimally Suppressing Extracerebral AADC Enzyme Activity—Toward Individualizing Carbidopa Therapy in Parkinson s Disease”, J Parkinsons Dis., vol. 2, No. 4,…
[cited by applicant]
Modak, “Breath biomarkers for personalized medicine”, Personalized Medicine, vol. 7, No. 6, 2010, pp. 643-653.
[cited by applicant]
O'Hara et al., “Limonene in exhaled breath is elevated in hepatic encephalopathy,” Journal of Breath Research, 10 (2016) 046010, 11 pages.
[cited by applicant]
Opdam et al., “The use of the 13C-dextromethorphan breath test for phenotyping CYP2D6 in breast cancer patients using tamoxifen: association with CYP2D6 genotype and serum endoxifen levels,” Cancer Chemother. Pharmacol.…
[cited by applicant]
Opdam et al., “Further Characterization of a 13C-dextromethorphan breath test for CYP2D6 phenotyping in breast cancer patients on tamoxifen therapy,” J. Breath Res. Apr. 2015. 20; 9(2):026003, Chapter 5, pp. 92-105.
[cited by applicant]
Owlstone Medical, “Targeted breath analysis: exogenous volatile organic compounds (EVOC) as targeted metabolic proves in Breath Biopsy,” Nov. 8, 2018, 49 pages.
[cited by applicant]
Penning, “The aldo-keto reductases (AKRs): Overview,” Chemico-Biological Interactions, vol. 234, Oct. 7, 2014, pp. 236-246.
[cited by applicant]
Von Grafenstein et al., “Precursors for cytochrome P450 profiling breath tests from an in silico screening approach,” J. Breath Res. 8 (2014) 046001, 14 pages.
[cited by applicant]
GB Search Report for GB Application No. 1814346.1, titled “Diagnosis of Cancer,” mailed on Mar. 25, 2019.
[cited by applicant]
PCT International Search Report and Written Opinion for International Application No. PCT/GB2019/052468, titled “Diagnosis of Cancer,” mailed on Dec. 3, 2019.
[cited by applicant]
Database WPI, Week 200377, Jul. 30, 2003, Thomson Scientific, London, GB, XP002795937.
[cited by applicant]
Database WPI, Week 201631, Mar. 16, 2016, Thomson Scientific, London, GB, XP002795938.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/GB2019/051381, entitled Method to Evaluate Metabolic Activity of Liver Enzymes, consisting of 17 pages. Date Mailed: Sep. 19, 2020.
[cited by applicant]
Fernandez Del Rio, R., et al, “Volatile Biomarkers in Breath Associated With Liver Cirrhosis—Comparisons of Pre- and Post-liver Transplant Breath Samples”, Ebiomedicine, vol. 2, No. 9, pp. 1243-1250 (2015).
[cited by applicant]
Chang, M., et al., “Interphenotype differences in disposition and effect on gastrin levels of omeprazole—suitability of omeprazole as a probe for CYP2C19,” Br. J. Clin. Pharmacol. 39, 511-518 (1995).
[cited by applicant]
De Kesel, P.M.M., et al., “Alternative Sampling Strategies for Cytochrome CYP450,” Phenotyping. Clin. Pharmacokinet. 55, 169-184 (2016).
[cited by applicant]
Lin, Y.S., et al., “In-vivo phenotyping for CYP3A by a single-point determination of midazolam plasma concentration. Pharmacogenetics,” 11, 781-791 (2001).
[cited by applicant]
Ned Mmsc Phd, R.M., “Genetic testing for CYCYP450 polymorphisms to predict response to clopidogrel: current evidence and test availability,” Application: pharmacogenomics. PLoS Curr. 2 (2010).
[cited by applicant]
Ou-Yang, D.S., et al., “Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population,” Br. J. Clin. Pharmacol. 49, 145-151 (2000).
[cited by applicant]
Pijls, K.E., et al., “Critical appraisal of 13 C breath tests for microsomal liver function: aminopyrine revisited,” Liver Int. 34, 487-494 (2014).
[cited by applicant]
Sachse, C., et al., “Cytochrome CYP450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences,” Am. J. Hum. Genet. 60, 284-295 (1997).
[cited by applicant]
Samer, C.F., et al., “Applications of CYCYP450 testing in the clinical setting,” Mol. Diagn. Ther. 17, 165-184 (2013).
[cited by applicant]
Tanaka, E., et al., “How useful is the “cocktail approach” for evaluating human hepatic drug metabolizing capacity using cytochrome CYP450 phenotyping probes in vivo?” J. Clin. Pharm. Ther. 28, 157-165 (2003).
[cited by applicant]
Thacker, D.L., et al., “Is (+)-[13 C]-pantoprazole better than (±)-[ 13 C]-pantoprazole for the breath test to evaluate CYP2C19 enzyme activity?,” J. Breath Res. 7, 16001 (2012).
[cited by applicant]
Thakur, M., et al., “Review of evidence for genetic testing for CYCYP450 polymorphisms in management of patients with nonpsychotic depression with selective serotonin reuptake inhibitors,” Genet. Med. 9, 826-835 (2007).
[cited by applicant]
Zanger, U.M., et al., “Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation,” Pharmacol. Ther. 138, 103-141 (2013).
[cited by applicant]
Great Britain Search Report, Application No. GB1808062.2, Date of Search: Dec. 12, 2018, 5 pages.
[cited by applicant]
GB Search Report for GB Application No. 1814350.3, titled “Diagnosis of Cancer,” mailed on Feb. 20, 2019.
[cited by applicant]
Restriction Requirement from U.S. Appl. No. 17/055,914, consisting of 5 pages. Dated Apr. 26, 2023.
[cited by applicant]
Final Rejection Mailed on May 30, 2024, entitled “Method to Evaluate Metabolic Activity of Liver Enzymes” for U.S. Appl. No. 17/055,914, 15 page(s).
[cited by applicant]
Masyita et al. Food Chemistry, entitled “Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives,” X13, 100217, 1-14 (Ye…
[cited by applicant]
Bacanli et al. The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin, Food and Chemical Toxicology, 2015, 81, 160-170 (Year: 2015).
[cited by applicant]
Barski et al Drug Metab. Rev., 2008, 40, 553-624 (Year: 2008).
[cited by applicant]
EP Response to Office Action dated Nov. 27, 2023, EP Application 19766318.0, entitled Diagnosis of Cancer, Applicant Owlstone Medical Limited, 4 pages.
[cited by applicant]
Fernandez del Rio et al. EBioMedicine, 2015, 2, 1243-1250 (Year: 2015).
[cited by applicant]
Goh et al. PLOS One, 2017, 12, 1-16 (Year: 2017).
[cited by applicant]
Hung et al., Prognostic significance of AKR1B10 in patients with resected lung adenocarcinoma, Accepted Aug. 13, 2018, Thoracic Cancer, 1492-1499, 9, Retrieved Jun. 27, 2018.
[cited by applicant]
Lu et al., Diagnostic value of aldo-keto reductase family 1 member B10 in human nasopharyngeal carcinoma, Accepted Aug. 21, 2023, Molecular and Clinical Oncology, 7 pages, 19:89.
[cited by applicant]
Non-Final Office Action received for U.S. Appl. No. 17/055,914, mailed on Nov. 6, 2023, 16 pages.
[cited by applicant]
Abruzzese F. et al., “Lack of correlation between mRNA expression and enzymatic activity of the aspartate aminotransferase isoenzymes in various tissues of the rat”, FEBS Letters, vol. 366, No. 2-3, Jun. 12, 1995, pp. 1…
[cited by applicant]
Chang T. K. et al., “Real-Time Polymerase Chain Reaction Analysis CYP1 B1 Gene Expression in Human Liver”, Review of Economic Dynamics, vol. 71, No. 1, Jan. 1, 2003, pp. 11-19.
[cited by applicant]
Ferreira Leal, Mariana et al., “Targeting tumour-associated aldo-keto reductase activity with exogenous volatile organic compound (EVOC) Probes to detect lung cancer”, Jun. 20, 2022, pp. 1-1.
[cited by applicant]