Molecular analysis of tumor samples
This invention relates to methods for diagnosing cancer, e.g., cancer of epithelial origin, by detecting the presence of tumor cells in a sample, based (at least in some embodiments) on the quantification of levels of four biomarkers, MUC1, EGFR, EpCAM, and HER2. In some embodiments, the methods are performed using diagnostic magnetic resonance (DMR), e.g., with a portable relaxometer or MR imager.
1. A method for treating an intra-abdominal tumor in a subject, the method comprising:
obtaining a sample from the subject, wherein the sample is not from breast or lung tissue;
detecting levels of biomarkers consisting of MUC-1, HER2, EGFR, and EpCAM in the sample by contacting the sample with antibodies or antigen-binding fragments thereof that bind to MUC-1, HER2, EGFR, and EpCAM and are labeled with superparamagnetic cross-linked iron oxide (CLIO) nanoparticles having a hydrodynamic diameter of 28.8 nm;
comparing the levels of MUC-1, HER2, EGFR, and EpCAM in the sample to reference levels; and
administering a treatment for cancer to a subject who has levels of MUC-1, HER2, EGFR, and EpCAM above the reference levels.
2. The method of claim 1 , wherein a single undivided sample is contacted with a mixture of antibodies, or antigen-binding fragments thereof, that bind to MUC-1, HER2, EGFR, and EpCAM, simultaneously.
3. The method of claim 1 , wherein the sample is subdivided into at least four subparts, and each antibody, or antigen-binding fragment thereof, that binds to MUC-1, HER2, EGFR, or EpCAM is contacted with a single subpart.
4. The method of claim 1 , wherein the levels of MUC-1, HER2, EGFR, and EpCAM are detected using diagnostic magnetic resonance (DMR) or direct magnetic detection.
5. The method of claim 1 , wherein the sample comprises blood or a subfraction thereof.
6. The method of claim 1 , wherein the sample comprises a biopsy sample.
7. The method of claim 6 , wherein the biopsy sample is a fine needle aspirate (FNA), endoscopic biopsy, or core needle biopsy.
8. The method of claim 1 , wherein the sample comprises cells from the pancreas, prostate, kidney, stomach, esophagus, bladder, endometrial, cervix, biliary, thyroid, ovary or colon of the subject.
9. The method of claim 1 , wherein the intra-abdominal tumor is from a pancreas, prostate, kidney, stomach, esophagus, bladder, endometrial, cervix, biliary, thyroid ovary or colon tumor.
10. The method of claim 1 , wherein the treatment for cancer comprises one or more of surgical treatment, chemotherapy, immunotherapy, and/or radiotherapy.
11. The method of claim 1 , wherein the antibodies or antigen-binding fragments thereof are linked to the CLIO nanoparticles via transcyclooctene (TCO)/tetrazine (Tz) chemistry.