Methods for the detection and treatment of lung cancer
View Patent ↗Provided are methods and related kits for detection of early stage lung cancer, and determination of risk of harboring lung cancer.
1 . A method of determining the risk of a subject for harboring lung cancer and treating lung cancer, comprising
(a) measuring a level of biomarkers in a biological sample obtained from the subject, wherein the biomarkers comprise diacetylspermine (DAS), CEA, CA125, CYFRA21-1, and Pro-SFTPB, and wherein the biological sample is collected prior to a diagnosis of lung cancer;
(b) combining the measured levels into a biomarker-based risk score, wherein the biomarker-based risk score is calculated using logistic regression analysis and wherein the subject's biomarker-based risk score is elevated relative to a healthy subject;
(c) administering a computerized tomography (CT) scan or other imaging modality to the subject having the elevated biomarker-based risk score;
(d) classifying the subject as lung cancer positive based on the increased risk of having lung cancer quantified in step (b) and the imaging results obtained in step (c); and
(e) administering to the lung cancer positive subject a therapeutically effective amount of a treatment for the lung cancer comprising surgery, chemotherapy, immunotherapy, radiation therapy, targeted therapy, or a combination thereof.
2 . The method of claim 1 , wherein the lung cancer is non-small cell lung cancer, adenocarcinoma or squamous cell cancer.
3 . The method of claim 1 , wherein the lung cancer is diagnosed at or before the borderline resectable stage or at the resectable stage.
4 . The method of claim 1 , wherein the biological sample is selected from blood, plasma, and serum.
5 . The method of claim 1 , wherein the measuring of CEA, CA125, CYFRA21-1, pro-SFTPB, and DAS levels is made at substantially the same time or in a stepwise manner.
6 . The method of claim 1 , wherein measuring the level of biomarkers of CEA, CA125, CYFRA21-1, pro-SFTPB, and DAS comprises the use of one or more reporter molecules; and/or one or more surfaces capable of binding one or more biomarkers; and/or one or more relay molecules capable of binding one or more biomarkers.
7 . The method of claim 6 , wherein at least one of the surfaces is the surface of a solid particle.
8 . The method of claim 7 , wherein the solid particle is a bead.
9 . The method as recited in claim 6 , wherein at least one of the reporter molecules is linked to an enzyme, or wherein at least one of the reporter molecules provides a detectable signal.
10 . The method as recited in claim 9 , wherein the detectable signal is detectable by a method selected from UV-visible spectroscopy, mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, proton NMR spectroscopy, nuclear magnetic resonance (NMR) spectrometry, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), correlation spectroscopy (COSy), nuclear Overhauser effect spectroscopy (NOESY), rotating frame nuclear Overhauser effect spectroscopy (ROESY), LC-TOF-MS, LC-MS/MS, and capillary electrophoresis-mass spectrometry.
11 . A method of treating a subject suspected of harboring lung cancer, comprising
(a) analyzing the subject for risk of harboring lung cancer with a method comprising:
(b) measuring a level of biomarkers in a biological sample obtained from the subject, wherein the biomarkers comprise diacetylspermine (DAS), CEA, CA125, CYFRA21-1, and Pro-SFTPB, and wherein the biological sample is collected prior to a diagnosis of lung cancer;
(c) combining the measured levels into a biomarker-based risk score, wherein the biomarker-based risk score is calculated using logistic regression analysis and wherein the biomarker-based risk score classifies the subject as being at risk of harboring lung cancer when the biomarker-based risk score is elevated in the subject relative to a healthy subject;
(d) classifying the subject as lung cancer positive based on the increased risk of having lung cancer quantified in step (c); and
(e) administering to the lung cancer positive subject a therapeutically effective amount of a treatment for the cancer.
12 . The method of treating of claim 11 , wherein the treatment is surgery, chemotherapy, immunotherapy, radiation therapy, targeted therapy, or a combination thereof.
13 . The method of claim 11 , wherein the lung cancer is adenocarcinoma or squamous cell cancer.
14 . The method of claim 11 , wherein the lung cancer is diagnosed at or before the borderline resectable stage or at the resectable stage.
15 . The method of claim 11 , wherein the biological sample is selected from blood, plasma, and serum.
16 . The method of claim 11 , wherein the measuring of CEA, CA125, CYFRA21-1, pro-SFTPB, and DAS levels is made at substantially the same time or in a stepwise manner.
17 . The method of claim 11 , wherein measuring the level of biomarkers of CEA, CA125, CYFRA21-1, pro-SFTPB, and DAS comprises the use of one or more reporter molecules; and/or one or more surfaces capable of binding one or more biomarkers; and/or one or more relay molecules capable of binding one or more biomarkers.
18 . The method of claim 17 , wherein at least one of the surfaces is the surface of a solid particle.
19 . The method as recited in claim 18 , wherein the solid particle is a bead.
20 . The method as recited in claim 17 , wherein at least one of the reporter molecules is linked to an enzyme; or wherein at least one of the reporter molecules provides a detectable signal.
21 . The method as recited in claim 20 , wherein the detectable signal is detectable by a method selected from UV-visible spectroscopy, mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, proton NMR spectroscopy, nuclear magnetic resonance (NMR) spectrometry, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), correlation spectroscopy (COSy), nuclear Overhauser effect spectroscopy (NOESY), rotating frame nuclear Overhauser effect spectroscopy (ROESY), LC-TOF-MS, LC-MS/MS, and capillary electrophoresis-mass spectrometry.