Optimizing Chemotherapy Results

Novel diagnostic tests to determine generic response to chemo

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With the advent of personalized medicine, which targets individualized treatment and care based on personal and genetic variation, the treatment options for cancer patients are rapidly emerging. Tests and devices that reliably track treatment response help clinicians decide whether to continue with a particular anticancer drug or to try another option.

New avenues of tracking chemotherapy response on an individual basis include the ATC chip, developed by Massachusetts General Hospital (MGH) investigators, MDxHealth's PredictMDx test for Glioblastoma and Saladex Biomedical's MyCare portfolio of exposure optimization tests.

Personalized Treatment for Cancer Patients
MDxHealth's PredictMDx for Glioblastoma (MGMT) test, included in the 2013 National Comprehensive Cancer Network (NCCN) Senior Adult Oncology Guidelines, provides valuable information to oncologists seeking to provide personalized treatment of elderly patients with glioblastoma. MDxHealth is a molecular diagnostics company that develops and commercializes advanced epigenetic tests for cancer assessment and the personalized treatment of patients.

"The MGMT assay determines the methylation status of the MGMT gene in tumor tissue," explained Wim Van Criekinge, PhD, chief scientific officer of MDxHealth and professor of bioinformatics at the University of Ghent in Belgium. "If the MGMT gene is methylated, cancer patients have shown improved response to alkylating drug therapy."

Glioblastoma, the most common and most aggressive malignant primary brain tumor in humans, typically kills most patients within 12 to 18 months of diagnosis. "It's important for doctors to try to get the right treatment to the right patient as soon as possible," Criekinge said.

Clinical trial results have demonstrated that PredictMDx for Glioblastoma can help oncologists identify glioblastoma patients who are likely to respond to alkylating agents, the most commonly used class of brain cancer drugs.

Many studies confirm the prognostic value of the PredictMDx test in glioblastoma. "This methylated gene test is also attractive for new brain cancer drug developers since they can more easily target their new drugs to the patients who usually do not respond to the traditional alkylating agent drug regime," Criekinge said.

Alkylating agents are broadly used in many solid tumors with varying success (especially over time), which illustrates the need for predictive biomarkers, according to Criekinge. "Given that MGMT is methylated in many different tissue types, it's likely that future research will show that MGMT methylation can be used as a predictor of response for cancer patients getting alkylating neoplastic agents," he stated. MDxHealth is exploring the test's application in other treatment regimens and other cancer types in collaboration with a number of pharmaceutical partners.

Are Liquid Biopsies on the Rise?
The ATC chip, developed by Massachusetts General Hospital (MGH), isolates and identifies tumor cells from ascites, an accumulation of fluid in the abdomen that often occurs in abdominal cancers. Designed to simplify the monitoring of patients' response to treatment for ovarian cancer and other malignancies, the microchip-based device was developed by investigators who work in the MGH Cancer Center and the Center for Systems Biology.

Because tumor recurrence typically begins before metastases become visible on imaging studies, MGH investigators are evaluating the use of liquid biopsies to identify tumors at a very early stage, monitor them for metastasis, and detect signs of early treatment resistance.

According to the investigators, ascites fluid from ovarian cancer patients is introduced through a filter into an inlet holding magnetically labeled benign cells. The remaining fluid passes through a microchip containing microwells where antibody-labeled tumor cells are captured for collection, imaging and additional analyses.

MGH representatives believe the ability to reliably track treatment response helps physicians decide whether to continue a particular anticancer drug or try another option. MGH has planned large-scale production of the ATC chip, and if future studies uncover the same results, the device's low cost and ease of use could be attractive in the treatment of ovarian cancer.

Chemotherapy Dosing
Developed in the 1900s, the current standard of care to dose chemotherapy drugs uses body surface area. Saladax Biomedical Inc.'s MyCare Diagnostics are designed to improve the efficacy of existing drugs by helping oncologists make informed decisions about drug dose adjustments for each individual patient, with the goals of maximizing the therapy's effectiveness and limiting its potential side effects. Specific dose adjustment algorithms guide the drug concentration prescribed for the next treatment cycle.

Saladax Biomedical currently offers three MyCare immunoassays to customize chemotherapy for better cancer care: My5-FU, MyPaclitaxel, and MyDocetaxel. My5-FU measures a patient's exposure to 5-Fluorouracil (5-FU), a chemotherapy commonly used to treat colorectal, breast and head and neck cancers.

MyPaclitaxel measures a patient's exposure to paclitaxel, a chemotherapy commonly used to treat breast, non-small cell lung cancer (NSCLC), ovarian and digestive tract cancers. Finally, MyDocetaxel measures a patient's exposure to docetaxel, a chemotherapy used to treat breast cancer, NSCLC, and digestive tract, prostate and head and neck cancers.

Rebecca Mayer Knutsen is on staff at ADVANCE. Contact: rknutsen@advanceweb.com

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