Prostate Cancer

Prostate cancer is the most common male malignancy in the United States: it is estimated that 192,280 new cases of prostate cancer will be diagnosed in 2009 alone. Over the past 25 years, dramatic improvements have been made in patient survival of this disease; in fact, the 5-year survival rate has increased from 69% to nearly 99%. However, once the cancer has spread, or "metastasized," the disease is fatal. Currently, no eff ective treatment is currently available. That is why prostate cancer remains the second leading cause of cancer death in American males, and an estimated 27,360 patients will lose their battle to the disease this year, dying predominantly from metastatic prostate cancer.

Patients with late stage prostate cancer may benefit from hormone therapy (androgen ablation), which removes the main source of fuel to tumor growth by suppressing male hormones (androgens). Unfortunately, patients ultimately become non-responsive to this treatment after a few years, resulting in uncontrolled disease status and patient death. New and more effective treatments must be developed quickly to address this critical issue.

Research

NFCR is currently supporting scientists whose research is focused on unraveling the root causes of prostate cancer metastasis and developing new and effective treatment for patients with metastatic prostate cancer. Here are some highlights:

NFCR Project Director Paul B. Fisher, M.Ph., Ph.D.
Virginia Commonwealth University School of Medicine, Richmond, VA

NFCR Project Director Paul B. Fisher, M.Ph., Ph.D., has developed an innovative gene therapy to treat prostate cancer - especially metastatic prostate cancer, which aff ects 60% of patients. This new therapeutic is a genetically reprogrammed virus, called "Cancer Terminator Virus" (CTV). CTV is designed to specifi cally infect tumor cells and destroy them by replicating itself within the cells. Th e secret of restricted tumor targeting lies in a special control system employed in CTV. Dr. Fisher's therapeutic virus employs a special gene element he discovered earlier which can only turn on virus replication in tumor cells, but not in normal cells. Once turned on, the virus copies itself inside a tumor cell and eventually causes cell death. On the other hand, the normal cells are prevented from being harmed because CTV can not replicate in them. This smart control system ensures that this small biological killing machine only fi res on tumor cells.

To further improve its killing eff ects, Dr. Fisher's team made the virus capable of producing another tumor-killing molecule, interferon gamma (IFNγ), when replicating in the tumor cells. IFNγ, a natural product of our immune system, can directly kill tumor cells as well as indirectly by eliciting immune responses. Intriguingly, both the viruses and IFNγ generated by them go and seek out tumor cells, whether localized or metastatic, and destroy them, without harming normal healthy cells in the body. This unique feature could make it especially useful for patients whose prostate cancer has already metastasized.

Currently, with NFCR support, Dr. Fisher is further testing CTV in prostate cancer cell lines and tumor models to confi rm its eff ects and observe potential side eff ects. In fact, this novel gene therapy has been tested in pancreatic cancer cells and tumor models and the results are very encouraging. If tests in the laboratory run well, CTV may soon be used in clinical studies and provide a more effective treatment to late stage prostate cancer patients. This new "lethal weapon" could be especially encouraging to patients whose prostate cancer has stopped responding to other treatments.

NFCR Project Director David Lyden, M.D., Ph.D.
Cornell University, New York, NY

NFCR Project Director, David Lyden, M.D., Ph.D., at Cornell University, has reasoned that the failure of current therapies to treat prostate cancer is due to the lack of deep down understanding of how cancer progresses and spreads in the body. Dr. Lyden has been looking into this issue from an important perspective - cancer microenvironments.

More and more scientific evidence suggests that cancer does not spread randomly in the body. Instead, it is a "seed and soil" matching process -- once the cancer cells (the "seed") get into the bloodstream, they must interact with a proper receptive environment (the "soil") at distant tissue or organs to prepare for the start of metastasis. Intriguingly, Dr. Lyden and his research team have found that prostate cancer cells produce growth factors which stimulate certain adult bone marrow immature (stem) cells to grow and enter the blood stream. These cells then travel to the tumor to support the growth of new blood vessels, which are a critical nutrient provider for rapid tumor growth.

Interestingly, Dr. Lyden discovered that these bone marrow stem cells also travel to distant organs and "prepare" them for the arrival of the metastatic tumor cells. Upon arrival at the distant organs, these bone marrow cells appear to interact with the surrounding tissues (cancer microenvironments) and change them to a more fertile nest for the tumor cells to attach and grow.

These intriguing findings suggest that these bone marrow stem cells may be an important factor for prostate cancer growth and metastasis. Dr. Lyden hypothesizes that the metastasis of prostate cancer is mediated by a well-defined sequence of events dependent upon the proliferation and mobilization of bone marrow stem cells.

With NFCR's support, Dr. Lyden will further explore how these bone marrow stem cells promote prostate cancer to grow and spread. This critical research may lead to breakthroughs in prediction and treatment of prostate cancer metastasis in patients. By measuring the stem cells identified in Dr. Lyden's lab, it is possible to predict which patients will be more prone to developing metastasis of their prostate cancer. Moreover, Dr. Lyden's team has identified key molecules on the surface of these stem cells and has developed drugs that specifically target those proteins and kill the stem cells, hence removing essential factors that support tumor metastasis. Without the necessary support and nourishment from these bone marrow cells, the tumor cells and especially those at metastatic locations will die. These drugs will be used in clinical trials for patients whose prostate cancer does not respond to any other therapies. If the clinical trials prove to be successful, these new drugs developed in Dr. Lyden's lab will be further tested and may soon be available to more prostate cancer patients. Dr. Lyden's work may change the entire scope of treating prostate cancer and lead to increased survival in late stage prostate cancer patients.

Posted in: Type of Cancer