A team of Houston Methodist researchers and clinicians received two grants totaling over $15.7 million from the Department of Defense (DoD) to accelerate a possible treatment for metastatic breast cancer.
Metastases to the lungs and liver are responsible for the vast majority of breast cancer deaths every year in the United States, yet there is no cure. Existing cancer drugs provide limited benefit due to their inability to overcome biological barriers in the body and reach the cancer cells in sufficient concentrations.
Mauro Ferrari, Ph.D, president and CEO of the Houston Methodist Research Institute, led teams over the past several years that developed a multi-component drug called an injectable nanoparticle generator polymeric doxorubicin (iNPG-pDox). The DoD grants provide funds for additional efficacy studies, which will then allow Jenny Chang, M.D., director of the Houston Methodist Cancer Center, and her team to offer the investigational therapy to approximately 50 triple negative breast cancer metastatic patients, possibly as early as the fall of 2018.
Ferrari and Haifa Shen, M.D., Ph.D., a lead scientist within the department of nanomedicine, conducted research that showed never before seen results in mice models with triple negative breast cancer that had metastasized to the lungs. A March 2016 Nature Biotechnology paper showed long-term cures for triple negative breast cancer with lung and liver metastases in about 50 percent of the preclinical cases. That's equivalent to about 24 years of long-term survival following metastatic disease for humans. At the same time, even for mice that were not cured, use of iNPG-pDox led to an unprecedented overall survival benefit.
"The biggest challenge in medical research is successfully translating a lab discovery into a viable treatment option for people. The cycle of a cure usually takes 17 years and costs billions of dollars. Our plan is to go from drug creation to Phase I and II clinical studies in five years," Ferrari said.
iNPG-pDOX has shown much less toxicity compared to conventional drugs that have adverse side effects to the heart. Due to the body's own defense mechanisms, most cancer drugs are absorbed into healthy tissue causing negative side effects, and only a fraction of the administered drug actually reaches the tumor. The Houston Methodist drug physically targets the cancer and enables sequential passage of the biological barriers to transport the iNPG-pDox into the heart of the tumor. The active drug is released inside the nucleus of the metastatic disease cell, avoiding the multidrug resistance challenges that current cancer therapies face when attempting to target tumors.
Chang, an internationally-known researcher and physician, has long focused on triple negative breast cancer, the most difficult kind of breast cancer to treat.
"Once we begin studies in patients, our goal will be to determine what dosage is needed to effectively kill the tumor and provide significant therapeutic benefit, before we can offer the investigational therapy to even more breast cancer patients," Chang said. "If iNPG-pDox bears out in our patients, this could mean a significant reduction in breast cancer deaths associated with lung and liver metastases, increased long-term survival, and enhanced quality of life."
The work is supported by the Department of Defense Breast Cancer Research Program/Congressionally Directed Medical Research Programs (W81XWH-17-1-0390 and W81XWH-17-1-0389).
To speak with Mauro Ferrari, Ph.D., or Jenny Chang, M.D., contact Gale Smith, Houston Methodist, at 281.627.0439 or firstname.lastname@example.org. For more information about Houston Methodist, visit houstonmethodist.org. Follow us on Twitter and Facebook.