Breast cancer is the most frequently diagnosed cancer in women. Ovarian cancer has a low survival rate. Developing breast and ovarian cancers shed transformed cells into the blood. More malignant breast and ovarian cancer cells appear in the blood at later stages. Early detection of circulating breast and ovarian cancer cells might improve diagnosis of early breast cancer and ultimately might reduce deaths from breast and ovarian cancer. We hypothesize that single nanotube-antibody junctions will detect circulating human breast and ovarian cancer cells in a drop of blood. Breast and ovarian cancer cell surfaces show high levels of insulin-like growth factor 1 receptor (IGF1R), human epidermal growth factor receptor 1 (Her1, EGFR), and Her2 (Erb-B2, neu), among others. We have already demonstrated antibody-specific detection of ER+/Her2- and ER+/Her2+ breast cancer cells suspended in a physiological buffer, and in fresh human blood. The single nanotube-antibody junctions detected the cancer cells within 60 seconds and stabilized by five minutes. We discovered significant changes in conductance of single nanotube-antibody junctions upon exposure to human MCF7 (ER+/Her2-) and BT474 (ER+/Her2+) breast cancer cells in physiological buffer or in fresh donor blood. Control cells did not change the device current. Breast cancer cells did not increase the current when PSMA or nonspecific antibodies were adsorbed to the single nanotube-antibody junctions. Hence, the current change required a specific antigen-antibody complex between the live, intact breast cancer cell suspended in blood, and the single nanotube-antibody junction. To date, this is the simplest method to detect live cancer cells in blood directly. We will test our hypothesis in three Specific Aims: Aim 1: We will determine the sensitivity limit for detection and capture of live, intact, human MCF7 (ER+/Her2-) and HCC1569 (ER-/Her2+) breast cancer cells, and human OVCAR5 ovarian cancer cells, among competing normal blood cells in drops of fresh human donor blood, as a function of mAb loading on the single nanotube junctions. Aim 2: We will determine the sensitivity limit for detection and capture of circulating breast and ovarian cancer cells in blood donated by metastatic breast and ovarian cancer patients, by IGF1R, EGFR, Her2, and EpCAM single nanotube-antibody junctions. Aim 3: We will design and build arrays of single nanotube-antibody junctions targeting the most common early markers IGF1R, EGFR, and Her2 simultaneously, vs. a nonspecific control. These experiments will provide a proof-of-principle for rapid noninvasive detection of circulating breast and ovarian cancer cells. Early detection of circulating breast and ovarian cancer cells might improve diagnosis and management of breast and ovarian cancer, and ultimately might reduce deaths from breast and ovarian cancer.
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