Assays for cancer patient monitoring based on levels of analyte components of the plasminogen activator system in body fluid samples

A method of monitoring cancer treatment, or efficacy thereof, in a cancer patient undergoing such treatment, comprising:

• (a) measuring levels of a complex of plasminogen activator (uPA) and uPA inhibitor PAI-1 (uPA:PAI-1 complex) in a plasma sample of the cancer patient;
• and
• (b) determining if the plasma levels of the uPA:PAI-1 complex increase during the cancer treatment compared to the plasma levels of the uPA:PAI-1 complex in normal controls, which is greater than about 293 pg/ml;
• wherein an increase in the plasma levels of the uPA:PAI-1 complex in the cancer patient compared to the plasma levels of the complex in normal controls during the monitoring period indicates one or more of the following:
• (i) cancer progression, (ii) a more severe stage of the cancer, or (iii) lack of response by the patient to the cancer treatment.

A method of monitoring cancer treatment, or efficacy thereof, in a cancer patient undergoing such treatment, comprising:

• (a) measuring levels of a complex of plasminogen activator inhibitor-1 (PAI-1) in a plasma sample of the cancer patient;
• and
• (b) determining if the plasma levels of PAI-1 increase during the cancer treatment compared to the plasma levels of PAI-1 in normal controls, which is greater than about 63 ng/ml;
• wherein an increase in the plasma levels of PAI-1 in the cancer patient compared with the plasma levels of PAI-1 in normal controls during the monitoring period indicates one or more of the following:
• (i) cancer progression, (ii) a more severe stage of the cancer, or (iii) lack of response by the patient to the cancer treatment.

A method of monitoring patient response to cancer therapy or treatment for a patient having metastatic cancer, comprising:

• (a) measuring levels of plasminogen activator (uPA) in a serum sample of the cancer patient prior to cancer therapy or treatment;
• (b) determining if the uPA levels of the patient are increased compared to the serum uPA levels in normal controls;
• the normal control serum uPA level being a value of 1924 pg/ml;
• and
• (c) establishing that the metastatic cancer patient having increased uPA levels compared with the uPA levels of normal controls has one or more of (i) ongoing or progressing metastasis;
• (ii) a likelihood of a decreased or poor response to cancer therapy or treatment;
• and (iii) a shorter survival outcome.

A method of determining if a cancer patient is a candidate for anti-plasminogen activation system cancer therapy, comprising:

• (a) measuring the level of plasminogen activator inhibitor-1 (PAI-1) or the level of a complex of plasminogen activator and plasminogen activator inhibitor-1 (uPA:PAI-1 complex) in a plasma sample of the cancer patient;
• (b) determining if either the level of PAI-1 or the level of uPA:PAI-1 complex in the plasma sample of the cancer patient is elevated compared to the normal level of PAI-1 or the normal level of uPA:PAI-1 complex in the plasma of normal controls;
• and
• (c) if said determining step (b) indicates that either said level of PAI-1 or said level of uPA:PAI-1 complex in the plasma sample of the cancer patient is elevated above said normal level of PAI-1 or above said normal level of uPA:PAI-1 complex, selecting the patient having elevated plasma PAI-1 level and/or elevated plasma uPA-PAI-1 complex level as a candidate for anti-plasminogen activation system therapy;
• wherein the normal plasma level of PAI-1 is a normal control value of about 63 ng/ml;
• and
• wherein the normal plasma level of uPA:PAI-1 complex is a normal control value of 293 pg/ml.

A method of monitoring cancer progression, or the efficacy of cancer treatment or therapy, in a cancer patient, comprising:

• (a) measuring the levels of one or more of the following plasminogen activator (PA) system analytes in a body fluid sample from the cancer patient:
• (i) uPA analyte in a serum sample, (ii) PAI-1 analyte in a plasma sample;
• and (iii) uPA:PAI-1 complex analyte in a plasma sample;
• and
• (b) determining if the sample levels of one or more of the uPA, PAI-1, or uPA:PAI-1 complex analytes in the cancer patient is increased or elevated during the cancer treatment or therapy compared to normal levels of each of the respective plasminogen activator system analytes in normal controls;
• wherein an increase or elevation in the sample levels of one or more of the uPA, PAI-1, or uPA:PAI-1 complex analytes in the cancer patient compared to the respective normal levels of the analytes during the monitoring period indicates one or more of the following:
• (i) cancer progression, (ii) a more severe stage of the cancer, or (iii) lack of response by the patient to the cancer treatment or therapy;
• and further wherein the cancer patient's sample uPA level is considered elevated or increased if it is above a normal uPA value of 1924 pg/ml;
• the cancer patient's sample PAI-1 level is considered elevated or increased if it is above a normal PAI-1 value of 63 ng/ml;
• and the cancer patient's sample uPA:PAI-1 complex level is considered elevated or increased if it is above a normal uPA:PAI-1 complex value of 293 pg/ml.