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Cutting-Edge Science: Personalized Drug Screening for Multiple ​Myeloma​

Published on 19th November

In the decades old “war” against cancer, scientist are increasingly developing ore and better ways to help doctors address the unmet medical needs of patients with cancer. In addition to identifying new genetic mutations in different cancers, scientists are developing new ways to sequence tumors.  However, drawing on novel scientific and technological development they are now finding methods to more accurately match specific cancer treatments tailored to the exact needs of the patient’s particular cancer. This approach is often referred to a personalized therapy or precision medicine.

This hard work is showing interesting results.  In the treatment of multiple myeloma for example, scientists have developed a personalize method for testing the effectiveness of drugs. With the new tests doctors may predict quickly and more accurately the best treatments for individual patients. The novel approach, developed by scientists at Washington University School of Medicine​ in St. Louis, also may aid patients with leukemia or lymphoma.

Photo 1.0: Pilar de la Puente, PhD (left), and Kareem Azab, PhD, of Washington University School of Medicine in St. Louis, have developed a screening tool that may predict quickly and more accurately the best treatments for individual patients with multiple myeloma. The 3-D tissue-engineered bone marrow (3DTEBM) cultures pictured were developed with bone marrow samples to help determine which treatments are most effective.
Photo 1.0: Pilar de la Puente, PhD (left), and Kareem Azab, PhD, of Washington University School of Medicine in St. Louis, have developed a screening tool that may predict quickly and more accurately the best treatments for individual patients with multiple myeloma. The 3-D tissue-engineered bone marrow (3DTEBM) cultures pictured were developed with bone marrow samples to help determine which treatments are most effective.

The new test is unique in many ways.  The screening method suggests which commonly prescribed multiple myeloma drug, or combination of drugs, a physician should consider first for a particular patient.  n addition to suggesting the optimal drug and drug combination, the novel test also suggests the optimum dosage. A study validating the new method will be published in the December 2015 issue of the journal Biomaterials and now is available online.[1]

More effective
The method also is being evaluated in a clinical trial involving patients with multiple myeloma. The results will indicate if the method is more effective than current screening methods. “Even before the patient completes all of the MRIs, CT scans and other imaging procedures following diagnosis, we can have a recommendation for which drug and dosage to prescribe,” explained Kareem Azab​, Ph.D, an assistant professor of radiation oncology at the School of Medicine and the Siteman Cancer Center​ member who leads the research. “The test results come in three to four days,”​ Azab continued.​​​​​

Incidence
Multiple myeloma is a cancer of the infection-fighting plasma cells, part of the immune system found mainly in bone marrow.  The immune system, designed to fight infections and other diseases and is made up of several types of cells that work together. Lymphocytes, including T cells and B cells, are the main cell types of the immune system.

The disease is relatively uncommon cancer. The lifetime risk of getting multiple myeloma in the United States is 1 in 143 (0.7%). However, according to according to the American Cancer Society, an estimated 26,850 U.S. residents will still be diagnosed with the disease and about 11,240 patients are expected to die of the disease this year, second most prevalent hematological malignancy. Half of multiple myeloma patients diagnosed in the earliest stage of the disease don’t survive beyond about five years after initial treatment because the cancer becomes resistant to treatments.[2]  And despite the introduction of novel treatments, the disease remains incurable.

Treatment options
Treating multiple myeloma is difficult because in 90% of cases there is no obvious genetic mutation that can be targeted with treatment. Also, standard drug screening methods do not adequately recreate the environment surrounding cancer cells growing in a particular patient’s body.  This makes these methods less reliable at predicting effective drug therapies.

“Based on the observed discrepancy between preclinical and clinical outcomes we’ve concluded that this can be attributed to the failure of classic two-dimensional culture models to accurately recapitulate the [very] complex biology of multiple myeloma as well as drug responses observed in patients,” noted Pilar de la Puente, Ph.D from the Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine.

Personalized drug screening
Azab and his colleagues, including De la Puente, the  hope that a more personalized approach will improve long-term patient outcomes. The method relies on 3-D tissue-engineered bone marrow cultures, also known as 3DTEBM, that Azab and his colleagues developed using myeloma patients’ bone marrow samples.

To more closely mimic outside the body what goes on within, scientists take small samples of a patient’s cells – cancerous and benign – and remodel them in the lab. This tumor “microenvironment” includes the cancer cells and other neighboring blood vessels, immune cells and other components whose interaction can help or inhibit the tumor cells’ growth.

Following this process, drugs are tested on the remodeled patient cells to determine which treatment is likely to be most effective.

This novel approach gauges the sensitivity of a patient’s cells to different drugs at any time in the course of the disease. “Therefore, as a patient’s multiple myeloma becomes more resistant to particular drugs, continued drug screening could suggest when to change therapies. This could save valuable time,” Azab explained. “Now we have a drug test that closely replicates what’s going on with a patient at any given moment. We think this method has a better chance of working than existing options,” he further noted.

New company
Azab and his colleagues have launched a new company, Cellatrix, in coordination with Washington University’s Office of Technology Management and BioGenerator, a nonprofit organization that helps area bioscience companies form.

The potential of the testing method has been noted by a number of medical and industry leaders. Later this year, Cellatrix will begin testing potential therapies on behalf of pharmaceutical companies. Azab’s team also is studying how well the screening method works for patients with leukemia or lymphoma.

When successful, Azab and his colleagues have won another battle in the ongoing struggle to conquer cancer, opening the way to better and more precise target treatment options.


Last Editorial Review: November 19, 2015

Photo: Pilar de la Puente, PhD (left), and Kareem Azab, PhD, of Washington University School of Medicine/St. Louis. (ADCs) Courtesy: © 2015 Robert Boston/Washington University School of Medicine/St. Louis. Used with permission.

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