Multiple myeloma is a progressive malignancy of bone-marrow plasma cells, is currently incurable and has a 5 year survival rate of 43%. Treatment typically involves high dose combination chemotherapy, but therapeutic response and patient survival are unpredictable and highly variable – attributed largely to the evolution of MDR in response to chemotherapy. The sooner that cancer cells evolving MDR can be detected, the sooner alternative treatment options can be initiated to prevent tumour re-occurrence and support quality of life. Currently, no procedures allow for a direct, non-invasive, continuous monitoring of MDR in this or any other cancer.
We have developed a liquid biopsy, which provides a non-invasive, personalised test for the routine monitoring of MDR in cancer patients (PCT/AU2018/050420 ‘Method for cancer prognosis’). The test scans a patient’s blood sample for a specific set of biomarkers, the evolution of which, correspond to disease progression and therapeutic response.
The test monitors a patient’s unique cancer phenotype by analysing biomarker ‘signatures’ on large extracellular vesicles isolated from myeloma patient blood samples. The signature includes; resistance markers, plasma cell markers, stem cell markers and phospholipid markers, the expression of which correspond to disease progression and therapeutic response. We provide evidence for a test that can simultaneously detect both disease burden and evolution of MDR in response to chemotherapy. We also provide evidence for the presence of a ‘stem cell-like’ subpopulation of vesicles in patients which are elevated in Multidrug resistant disease.
These results demonstrate that MDR in myeloma patients can be detected and monitored serially by analysing large extracellular vesicles in blood samples in the form of a liquid biopsy. This test has potential to complement existing clinical benchmarks used in diagnosis and staging of myeloma. Our test enables a personalised approach to disease management with potential to improve treatment success and survival in myeloma patients.
Funding
This work is supported by funds from SPARK Oceana and UTS Innovation Commercialisation fund to M.Bebawy.