A New study
published in the Journal of Clinical
Investigation suggests that administration of currently available
drugs can stop the spread of breast cancer to other parts of the body.
- Dasatinib, an FDA approved drug can target
cells that play a crucial
role in the spread of breast cancer before metastasis occurs.
- The drug which is a src kinase
inhibitors was found
to decreases tumor progression and
metastasis in mice by up to five times.
- The inhibitors should be
administered when before the cancer cells have
not metastasized or during early metastasis.
study conducted by research teams at University of California San Diego School
of Medicine and Moores Cancer Center report that the drugs target stem-like tumor cells that play a key role in cancer
Stem-like tumor cells
tumor cells play their role during the spread of cancer, before metastasis.
They are responsible for
cancer progression and recurrence as these are those
that remain and grow in the body despite even after cancer
treatments such as chemotherapy
and radiation. The new study suggests
that co-expression of cell surface receptor integrin
αvβ3 and transcription factor Slug identifies these rare cells in
patient-derived tumor samples
. Moreover, this co-expression is observed in
nearly 20% of the primary breast cancer cases.
Tumor samples were
collected from the Women's Healthy Eating and Living clinical trial. The
research team identified stem-like tumor cells by
recognizing their characteristic low levels of p53 upregulated modulator of
"If we are going to
make a difference in the number of people who die of breast cancer
we need to stop metastasis and we think
we have a way to do it," said Jay S. Desgrosellier, PhD, senior author and
assistant professor in the Department of Pathology at UC San Diego School of
‘Administering kinase inhibitors can block αvβ3 signaling and prevent the breast cancer from spreading.’
Suppression of the
tumor suppressor protein involved PUMA expression is crucial for tumor
progression and the αvβ3/Src/Slug signaling pathway is the means by which this
is achieved. However, the study found PUMA levels
can be increased by either genetically disrupting this pathway, or by using the
FDA-approved Src kinase inhibitor dasatinib In mice experiments, the overexpression
of PUMA decreased tumor progression and metastasis by five times
The study also reports that increase in PUMA levels only target
stem-like tumor cells that are beginning to spread and have no effect on the
cells of the primary tumor cells.
introducing a potential new therapeutic approach that is particularly useful in
preventing new metastatic disease from forming," said Desgrosellier.
"The inhibitors should be given when cancer cells have not metastasized or
during early metastasis, when cells are still circulating. Disseminated cells
are more sensitive to PUMA expression because they are already stressed. The
cells in primary tumors are already established and are not affected by the
- Qi Sun, Jacqueline Lesperance, Hiromi Wettersten, Elaine Luterstein, Yoko S. DeRose, Alana Welm, David A. Cheresh, Jay S. Desgrosellier. Proapoptotic PUMA targets stem-like breast cancer cells to suppress metastasis. Journal of Clinical Investigation, 2017; DOI: 10.1172/JCI93707