CureSearch for Children's Cancer funds and supportstargeted and innovative children's cancer research with measurableresults, and is the authoritative source of information and resourcesfor all those affected by children's cancer.
Ewing sarcoma survival rates have reached a plateau in recent decades – overall the five-year survival rate is just 60%. Survival rates for patients with metastatic disease or who relapse are much lower. This plateau suggests that conventional treatment regimens have reached the limit of their efficacy and underscores the need to develop new or improved therapies. Development of such therapies might also avoid or mitigate the adverse side effects of conventional chemotherapy.
The Nick Currey Fund is currently supporting five research projects aimed at improving outcomes for children diagnosed with Ewing sarcoma.
In a study being conducted at Georgetown
University's Lombardi Comprehensive Cancer
Center since September 2010, a small molecule
drug specific to Ewing Sarcoma is being
developed. The project is looking at how
combinations of a drug specific to Ewing
Sarcoma, YK-4-279, and current cancer therapies
interact synergistically. The findings from the
study will help inform how the drug may be
used as a therapy. Furthermore, the study may
help define how YK-4-279 works inside Ewing
Based on data suggesting that alterations in
two specific genes, p53 and pl6, may help
predict future outcomes for patients with Ewing
sarcoma, Drs. Stephen Lessnick and Julia Bridge
are evaluating how often 2 specific genes are
altered in a large cohort of tumor specimens,
and whether these alterations predict patient
outcomes. As part of the study, the investigators
will also "amplify" tumor DNA to allow them to
study the genes and create an important resource
for other investigators studying this disease. If
this study supports the idea that p53 and/or pl6
alterations can predict patient outcome, these
tests might then be incorporated in future clinical
trials for patients with Ewing sarcoma.
Dr. Lawlor's lab previously identified that
Ewing sarcoma cells survive when deprived
of oxygen. Dr. Lawlor and colleagues
discovered that suppression of the potassium
ion channel Kv1.5 is, at least in part,
responsible for this abnormal cell survival.
Kv1.5 is a type of protein in cells that moves
potassium out of cells. Therefore, Dr. Lawlor
hypothesizes that restoring expression of
the Kv1.5 channel in Ewing sarcoma cells
may inhibit their resistance to cell death
and lead to better outcomes for patients.
Dr. Lawlor and her team will study both
normal and cancer cells to understand Kv1.5
channel suppression in Ewing sarcoma. Cell
death under conditions of stress requires
potassium ions move out of the cell,
which is often blocked in cancer, leading
to abnormal cell survival. Understanding
how this response is disrupted in Ewing
sarcoma can lead to tools to reactivate it
and ultimately prevent survival of the most
therapy-resistant cells and thereby prevent
Using microarray technology, Dr. Schiffman
and his colleagues retrospectively examined
archived tissue samples from 40 patients
at the University of Utah, including tissue
from patients who had both relapsed and
metastatic disease. A gene called CEBPB
was found to be amplified in many patients
- instead of the normal two copies of the
chromosome, there were as many as 11.
Further research identified seven other
chromosomal regions in Ewing sarcoma
patients in which amplification or missing
genes occurred. Those with changes in
gene copy numbers are called Multifactor
Copy Number (MCN)-positive and those
without changes are called MCN-negative.
In comparing the findings to the patients'
clinical outcomes it was found that patients
who were MCN-negative had a 100% survival
rate over 12 years, compared to a 41%
survival rate over 12 years for those patients
who were MCN-positive.
The study is being expanded to examine
tissue samples from across the country and
determine if findings can be validated. If
they are, it may lead to a change in protocol
treatment for patients with Ewing sarcoma
as tumors could be examined at diagnosis
and therapy adjusted based on the MCN
status of individual patient tumors.
Bringing together data from multiple Ewing sarcoma studies with the hopes of funding overarching information to
develop targeted treatments, the Nick Currey Fund is funding statisticians working on five projects.
For more information please contact NickCurreyFund@CureSearch.org.