FIELD OF THE INVENTION

The present disclosure relates to methods that are useful in evaluating tumors in human samples.

BACKGROUND

The use of predictive and prognostic biomarkers paired with targeted cancer therapies may hold the key to reducing drug development time, improving drug efficacy, and guiding clinical decision making. While there have been advances in cancer treatment, chemotherapy remains largely inefficient and ineffective. One reason for the generally poor performance of chemotherapy is that the selected treatment is often not closely matched to the individual patient's disease. A personalized medicine approach that couples precise diagnostics with therapeutics might alleviate this problem.

Further complicating widespread application of chemotherapies is that subsets of patients are likely to incur life-threatening treatment-related toxicities. For example, tumor lysis syndrome (TLS) may cause a patient to be unable to receive a treatment for its cancer. Again, personalized medicine approaches seek to improve clinical outcomes by identifying patients likely to exhibit such toxicities and eliminate them from consideration for treatments likely to exhibit said toxicity.

Diagnostic approaches are needed that can predict drug toxicity, including susceptibility to TLS, and drug efficacy in a patient.

SUMMARY OF THE INVENTION

Accordingly, in one aspect, the present disclosure provides a method for determining an adverse response to one or more cancer treatments in a patient, comprising: determining a BH3 profile for the patient's cell specimen; and classifying the patient for likelihood of an adverse response to one or more cancer treatments. In some embodiments, the method for determining an adverse response to one or more cancer treatments in a patient comprises a) isolating a cancer cell or specimen from the patient; b) contacting the cancer cell or specimen with one or more BH3 peptides; c) detecting a signal that indicates mitochondrial membrane permeabilization e) determining a correlation between the mitochondrial membrane permeabilization and adverse events from treatment; and f) classifying the patient for likelihood to adverse events from treatment.

In another aspect, the present disclosure provides a method for determining a treatment response to one or more cancer treatments in a blood cancer patient, comprising: determining a BH3 profile for the patient's tumor or cancer cell specimen; and classifying the patient for likelihood of one or more of an adverse response to one or more cancer treatments and a therapeutic efficacy to one or more cancer treatments wherein a BH3 profile comprising BAD and/or PUMA is indicative of an adverse response to one or more cancer treatments and a BH3 profile comprising BIM and/or HRK is indicative of therapeutic efficacy to one or more cancer treatments. In some embodiments, the method for determining a treatment response to one or more cancer treatments in a patient comprises a) isolating a cancer cell or specimen from the patient; b) contacting the cancer cell or specimen with one or more BH3 peptides, c) detecting a signal that indicates mitochondrial membrane permeabilization; e) determining a correlation between the mitochondrial membrane permeabilization and adverse response to one or more cancer treatments and a therapeutic efficacy to one or more cancer treatments; and f) classifying the patient for likelihood to adverse response to one or more treatments and therapeutic efficacy to one or more cancer treatments. In some embodiments, mitochondrial membrane permeabilization after contacting the cancer cell or specimen with BAD and/or PUMA is indicative of an adverse response to one or more cancer treatments, and mitochondrial membrane permeabilization after contacting the cancer cell or specimen with BIM and/or HRK is indicative of therapeutic efficacy to one or more cancer treatments. The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, illustrative methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

