findings of the study appear in the journal Oncogene.
may soon be tested in a clinical trial as a
for Ewing sarcoma.
‘FDA-approved Clofarabine could soon be tested as a possible treatment for Ewing sarcoma’
The Search For A
Possible Drug For Ewing Sarcoma Among Existing Compounds
does not have many effective
treatment options available currently and finding
one for the disease has also been
a considerable challenge. Additionally, discovering a new drug for any disease from
a tedious process
can take a
very long time, with the results not measuring
up to expectations sometimes.
Hence, the research team
easier and quicker method
to find new treatments
for a disease by sifting through already existing drugs
(to treat other
diseases) to try and see if any of them would be effective in the
second condition (in this instance Ewing sarcoma) as well.
Finding a Drug That Can Bind To Ewing Sarcoma Protein CD99
Üren, an associate professor of molecular biology at Georgetown
University School of Medicine and a member of Georgetown Lombardi collaborated
with a team of investigators from Georgetown Lombardi, and from Italy and
Turkey to find a drug for Ewing sarcoma
specifically targeting CD99
is a protein expressed by Ewing sarcoma cells that aids in tumor growth and progression
. It is a transmembrane
protein that spans across the thickness of the cell
membrane with one end sticking out of the cell and the other end placed inside
the cell. In fact, the diagnosis of Ewing sarcoma depends not only
on the microscopic appearance of the cancer cells but also
the CD99 protein on the tumor cells by specialized techniques.
- The team searched the
National Cancer Institute database
of 2,607 compounds to find one that could be potentially beneficial in
Ewing sarcoma patients.
of the conventional tailor-made approach of finding a compound that would fit into
a pre-selected slot or groove on the CD99 protein, the team looked for compounds that would bind
anywhere on CD99 and see what would happen.
- Although they found 150 compounds that could bind to CD99, only two demonstrated
a beneficial effect.
- One was clofarabine, a drug that was FDA-approved for
treating relapsed or refractory acute lymphoblastic
leukemia (ALL) in children alongwith at least two other types of treatment.
- The other was cladribine (Leustatin™) used to
treat hairy cell leukemia, B-cell chronic lymphocytic leukemia, and
multiple sclerosis, and FDA approved as well.
- When these agents bound to the CD99
protein, it was found that both of them dramatically reduced tumor growth in cell culture and animal studies,
but clofarabine destroyed
toxicities were noted (infertility, other cancers, heart
toxicity) with both agents, as the agents affect not only the external
aspect of CD99 but the interior of the cell as well, altering cellular DNA
metabolism and thus
producing the resulting toxicity.
According to Uren, "We believe it is sufficient to
act only on the outside of the protein to kill Ewing sarcoma cells. Therefore,
a derivative of clofarabine - just the part that latches onto CD99 without
activating it - would likely work very well in the treatment of Ewing
Merits of the Study
- The team believes that
clofarabine in its existing form can
soon be tested as a possible treatment for Ewing sarcoma in a
- Current study shows that inhibiting
CD99 protein can help
develop treatments for other cancers and immune disorders
that express this protein.
conclusion, if clofarabine is shown to be safe and effective in controlling and
destroying Ewing sarcoma cells, it may bring about a paradigm shift in the
management of Ewing sarcoma.
the words of Üren, "Our goal is to improve both survival and quality of
life for Ewing sarcoma patients, and this drug, when used in combination with
other therapies, may do the trick. Our work also provides the knowledge on how
to make safer derivatives with fewer side effects for Ewing sarcoma patients."
- CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis. - (https://www.ncbi.nlm.nih.gov/pubmed/20197622)
- Clofarabine - (https://en.wikipedia.org/wiki/Clofarabine)