NFCR Translational Research: Metastatic Cancer - NFCR

NFCR Translational Research: Metastatic Cancer

NFCR Translational Research: Metastatic Cancer

New Treatment for Advanced Cancers in Phase I Clinical Trial

Ronald A. DePinho, M.D. Univ. of Texas MD Anderson Cancer Center, Houston, Texas

STAT3 is a major signaling protein in cells. It is hyperactivated in over 50% of cancers. This results in abnormal cell growth, escape from our immune system, metastasis (spreading), and other cancer-associated processes. The development of drugs to target STAT3 effectively has been a challenge for the research community, earning it the label of ‘undruggable’. 

Ronald DePinho, M.D. and his colleagues used computer-based drug screening of hundreds of thousands of compounds to identify several candidates that inhibit STAT3 protein when tested in complex tumor models of breast and other various cancers.

NFCR support facilitated the final studies of the most promising inhibitor of STAT3. The new inhibitor drub is treating patients in an ongoing Phase I clinical trial to establish its safety and appropriate dose. Patients with advanced cancer may be eligible to enroll in the trial of this new treatment.


Detection of Advanced Cancer and Guiding Its Treatment:
Noninvasive Liquid Biopsy – Reaching Patients Soon

Daniel A. Haber, M.D., Ph.D. Massachusetts General Hospital Cancer Center, Boston, MA

A small number of circulating tumor cells (CTCs) may travel in a patient’s bloodstream among billions of healthy cells. CTCs are in the act of spreading – either from the primary tumor or a metastatic site.

With long-term support from NFCR and others, Dr. Daniel Haber and his team developed the CTC-iChip – a medical device to capture the few CTCs present in a standard blood sample from a patient. They developed methods to analyze the genes in CTCs, providing a liquid biopsy and an invaluable window into a patient’s cancer in real time. 

With the liquid biopsy, doctors may efficiently obtain critical information from their patient’s CTCs for life-saving treatment decisions in advanced cancer including:

  • Define genetic mutations causing resistance to cancer patient’s treatment.
  • Guide the use of immunotherapy and other patient treatments.

The CTC-iChip is currently in use in hospitals worldwide for research purpose. In the near future, the technology will be submitted to the FDA for required approval. Doctors can then use the CTC-iChip to obtain the critical information they need for important treatment decisions.


Multi-Action Gene Therapy in Development for Advanced Cancer

Paul B. Fisher, M.Ph., Ph.D. Virginia Commonwealth University, Richmond, VA

NFCR funding since 2008 helped Dr. Paul Fisher think “outside the box” to develop IL/24 gene therapy (IL/24 is from the Interleukin gene family of immune system modulators).

He engineered IL/24 gene to reach cancer cells — at all sites in the body — to commit suicide (normal way cells die). Healthy cells are unaffected by IL/24 gene’s effects. IL/24 gene modulates the immune system to kill cancer, inhibits blood vessel formation to tumors to starve them of vital blood supply, and sensitizes cancer to radiation, chemotherapy and immunotherapy. IL/24 gene therapy is effective in models of numerous types of advanced cancer including melanoma and colon, lung, bladder, prostate, liver, and pancreatic cancer, among other types.

Dr. Fisher is bringing IL/24 gene therapy to clinical trials to benefit patients. The gene therapy is advancing through pre-clinical research first as a new treatment for fatal brain cancer, GBM (glioblastoma). This would facilitate future trials of IL/24 gene therapy for other types of cancer.


Development of New Inhibitor of Cancer Invasion into Healthy Tissue and Metastasis

Paul B. Fisher, M.Ph., Ph.D. Virginia Commonwealth University, Richmond, VA

Invasion of cancer cells into healthy tissue is a hallmark property of cancer. MDA-9/Syntenin is a pro-invasion and pro-metastatic gene discovered by Dr. Paul Fisher with NFCR funds. With leading-edge chemistry and drug design techniques, his team developed the drug, PDZ1i, to inhibit invasion and metastasis properties of MDA-9/Syntenin. His team is developing PDZ1i for clinical trials. PDZ1i shows profound “anti-invasive” and “anti-metastatic” activity in models of liver, prostate, lung, brain, pancreas, and breast cancer and melanoma and neuroblastoma. PDZ1i works well with chemotherapy, radiation, or immunotherapy to kill cancer cells. NFCR funds are advancing the required pre-clinical research of PDZ1i to apply for the IND (Investigational New Drug) application and gain FDA approval for a Phase 1 clinical trial for the main type of liver cancer, hepatocellular cancer (HCC).  Success in the trial for HCC patients will facilitate development and future trials of PDZ1i treatment for other types of cancer.



Dr. Daniel Haber and his team are using the gene-editing tool, CRISPR, to identify and turn on or off the genes that regulate the ability of circulating tumor cells (CTCs) to metastasize from breast tumors. Several candidate genes have been identified. Ultimately, therapies will be developed that suppress the genes and give women greater hope for surviving the metastatic recurrence of breast cancer. This same approach can be utilized for other types of metastatic cancer.

Dr. Danny Welch and his team discovered DNA variabilities in mitochondria—the specialized cell part that makes energy from food. These variabilities may explain why racial susceptibilities to certain cancers exist and the ability of cancer to metastasize. This research may lead to a simple blood test to guide doctors in treating patients who are susceptible to metastasis and may need more aggressive treatment, or spare other patients of unnecessary harsh side effects.

Dr. Welch’s team also discovered eight genes that get turned off in cancer, as the cells become metastatic.  This research can lead to unique anti-metastasis therapeutics such as smaller proteins that ‘mimic’ the function of the active part of the turned-off gene and may arrest metastasis.