BACKGROUND AND CHALLENGES

Multiple myeloma (also known as myeloma) is a cancer originated from the plasma cell, a type of antibody-producing immune cells. With good medical attention, myeloma can be controlled at a stable status, but there is no cure with current treatment. Scientists and researchers are actively pursuing new and better treatment strategies to fight this disease more effectively. This goal is shared by two National Foundation for Cancer Research scientists, whose research projects hold promise in improving the available treatment or developing novel drugs against multiple myeloma.

SAVING MORE LIVES WITH BETTER TREATMENTS

Conquering the lethal complication of bone marrow transplantation. Bone marrow transplantation is a life-saving procedure commonly used in patients with myeloma following high-dose chemotherapy. High-dose chemotherapy wipes out cancerous cells, but it also destroys the normal blood-forming cells, which could kill the patients as well. Bone marrow transplantation is to replenish the vital blood-forming system in those patients. The bone marrow cells can be taken from the same patient (autologous transplants) or from another person (allogeneic transplants).

Research has shown that allogeneic (non-self) transplants lead to longer disease-free survival time and lower relapse rates in some myeloma patients compared to autologous (self) transplants. Despite these advantages, allogeneic transplantation is not commonly used since it may also cause a severe complication known as the Graft-versus-host disease (GVHD). In GVHD, a subset of the immune cells from the transplant is activated and mounts vigorous immunologic attacks to the patient (recipient). This side effect could be lethal, which greatly limits the clinical application of allogeneic bone marrow transplantation in patients with multiple myeloma and other diseases. NFCR Fellow Curt Civin, MD, at the University of Maryland School of Medicine (formerly at the Johns Hopkins University School of Medicine), is seeking ways to reduce the lethal side effects of allogeneic bone marrow transplantation, making this treatment safer and more beneficial to the patients.

Scientists found that when the anti-recipient immune cells in the transplant are activated and ready to attack, the molecular changes in the cell signaling pathways also render these cells susceptible to death. Dr. Civin and his team developed a unique strategy which takes advantage of this vulnerability and sends the anti-recipient immune cells to their suicidal path. This smart strategy also keeps intact the "recipient-friendly" cells in the transplant, which is important for successful blood replenishment in the patient.

With continued support from NFCR, Dr. Civin will further evaluate this exciting new approach in his research laboratory. Dr. Civin hopes to bring this promising treatment strategy to the patients' bedside in the near future, saving more lives of those with multiple myeloma and other diseases.

Developing a new class of multi-functional anti-cancer drugs. NFCR Project Director Dr. Michael Sporn, at Dartmouth Medical School, is a leading scientist in the field of new anti-cancer drug development. Dr. Sporn and his team of researchers have synthesized a new class of anti-cancer drugs, named synthetic triterpenoids, which have shown powerful preventative and/or treatment effects against multiple myeloma, leukemia, lung, liver, pancreatic and other types of cancer.

Triterpenoids are naturally synthesized in many plants, and some of them have been found to have weak anti-inflammatory and anti-cancer activity. Dr. Sporn and colleagues at the Dartmouth College hoped to generate a class of synthetic triterpenoids which have more powerful anti-inflammatory and anti-cancer property than their naturally born counterparts. Through a series of chemical analysis, compound synthesis and biological evaluation, the team nailed down a small group of synthetic triterpenoids (including CDDO, CDDO-Im, and CDDO-Me) that have shown potent, multi-functional activity. Depending on the dose, these compounds can suppress inflammation, inhibit cancer cell proliferation and induce cancer cell suicide in a variety of cancer cell lines, including multiple myeloma. These properties are important for prevention and treatment of multiple types of cancer.

Currently, two of the synthetic compounds have already entered Phase I clinical trials for treatment of patients with leukemia and solid tumors. With more laboratory and clinical tests on other types of cancer including multiple myeloma, this new class of anti-cancer compounds may soon reach patients' bedside for prevention and treatment of a variety of cancers.

INCUBATING NEW LIFE-SAVING APPROACHES IN THE LABORATORY

Unlike most other research funding agencies which typically support one project for a fixed, limited time period, NFCR has been supporting many of our scientists for as long as 20 or 30 years. NFCR began to fund Dr. Civin's research since 1997, and our support of Dr. Sporn's research started in 1999, when he just began his adventure on developing synthetic triterpenoids in his laboratory. Our decade-long support has allowed scientists to incubate their innovative ideas, evaluate and improve them over time, and eventually reach full blown breakthroughs which may help save tens of thousands of cancer patients' lives.

NEXT STEPS: HOW YOU CAN HELP

These NFCR-supported research projects hold great promise in developing new and better treatment to save more patients' lives from multiple myeloma. What our scientists need is research funding.  Please click here if you would like to make a donation.