What is Combating Metastases?
Metastatic cancer is the term used to describe any cancer that has spread from the area it started in to other areas of the body. For some types of cancer, metastasis is also called stage IV cancer, and metastatic cancers are often hard to control.
Cancer can spread to any part of the body, but the most common sites of metastasis are the bones, brain, liver and lungs. Although metastasis causes more than 90% of cancer-related deaths, it only receives less than 5% of research funding.
NFCR Research Highlights
Dr. Danny Welch and his team have discovered eight of the more than 30 known metastasis suppressor genes. Further research based on these discoveries may lead to the design of molecules that either prevent metastasis from happening or maintain metastatic tumors in a dormant state. They have also identified genetic changes that predict whether or not patients will develop metastasis. At least some of these genetic changes occur in mitochondria – where cells convert nutrients into energy. Mitochondrial DNA is present in every cell and is small enough to be rapidly analyzed, which means that a simple blood draw and analysis of mitochondrial DNA could be used to help treat patients.
Dr. Daniel Haber and his collaborators developed the CTC-iChip – an advanced micro-engineered device that captures extremely rare circulating tumor cells from the blood. Genetic testing on captured CTCs in a standard blood sample may give doctors a way to more effectively treat the tumor or stop it from spreading. Moreover, CTCs allow the response of treatments to be monitored in real-time. This device could dramatically improve treatment and diagnosis for metastatic breast cancer and other types of metastatic cancers.
With support from the NFCR AIM-HI Translational Research Initiative, Dr. Ronald DePinho and colleagues have developed a promising new drug that inhibits, STAT3, a major signaling protein in over 50% of cancers. STAT3 controls networks of genes for numerous cellular processes, including proliferation, survival, angiogenesis, metastasis, invasion, and immune escape. The drug is now in Phase 1 clinical trials to treat various types of advanced cancers.
Dr. Paul Fisher discovered a powerful cytokine, IL/24, or immune system modulator. IL/24 causes cancer cells in both primary and metastatic tumors to commit cell suicide (known as apoptosis). IL/24 gene therapy has other anti-cancer properties and it is effective in models of potentially all types of solid tumors. Dr. Fisher and Dr. Web Cavenee with support from NFCR’s AIM-HI Translational Research Initiative, are first advancing IL/24 gene therapy for the deadly brain cancer, glioblastoma (GBM).
Dr. Fisher also discovered the gene, MDA-9/ Syntenin, that promotes the deadly spread (metastasis) of many cancers. Dr. Web Cavenee and he developed an innovative candidate drug, PDZ1i, that blocks the gene’s signals for metastasis. The scientists are translating their research on PDZ1i treatment towards clinical trials to benefit patients.
The collaborative team of Dr. Paul Schimmel and Dr. Xiang-Lei Yang discovered one member of the family of enzymes involved in first step of protein synthesis in all living things, SerRS, is also a potent suppressor of cancer progression and metastasis and may also activate the immune system to fight cancer. This critical area of research may lead to novel therapeutic applications in brain, breast, esophageal, kidney, lung, rectal, and thyroid cancers.