“A major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance, specifically multidrug resistance (MDR),” explains Mary Bebawy, PhD. “MDR is especially problematic in the treatment of patients with incurable cancers, like multiple myeloma. Treatment typically involves high-dose combination chemotherapy, with which patient response is unpredictable and variable, due to the presence of multisite tumor infiltrates and the development of MDR.” With no clinical test available that enables routine testing of MDR in myeloma, Dr. Bebawy and colleagues sought to address this unmet clinical need.

For a study published in the Blood Cancer Journal, the researchers collected and tested blood samples from patients with and without multiple myeloma. With previous research suggesting that microparticles (MPs) could be used to determine disease burden, they analyzed blood for three MP markers of MDR: P-glycoprotein (P-gp), plasma-cell marker (CD138), and phosphatidylserine (PS). A small group of patients had their complete protein signature (P-gp, CD138, PS, and stem-cell marker [CD34]) assessed.

Elevated levels of P-gp+ and PS+ indicated disease progression and treatment unresponsiveness, while P-gp, PS, and CD34 were predominantly expressed in CD138 MPs in advanced disease. In particular, a dual-positive (CD138−P-gp+CD34+) population was elevated in aggressive/unresponsive disease. “CD138 cannot be considered a ‘static’ biomarker of multiple myeloma disease evolution, as the presence of a CD138 vesicle population increases in aggressive disease,” emphasizes Dr. Bebawy. “This has important implications in how we define the utility of biomarkers at each stage of disease.”

Dr. Bebawy notes that the “test has the potential to transform and benefit cancer care in many ways. Detecting MDR and disease progression routinely during treatment, patients are afforded personalized care, rationally guided by individual response. The presence of MDR may guide decision making around the adoption of alternative, more costly treatments, such as immunotherapies, to offer the best chance of treatment success for chemotherapeutic unresponsive patients. The test also provides capabilities in molecular characterization of disease through the biomarker panel. Specifically, this provides a fingerprint of the evolving disease in the marrow in response to treatment and opportunities for targeted therapy. Another tremendous benefit in having this test is in preventing unnecessary cytotoxic exposure by providing an assessment of predicted response.”

References

A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma
https://www.nature.com/articles/s41408-020-0304-7