Identifying and to establish the re-establishment of tumors.

 

 

       Identifying properties of Breast Cancer stem (CSCs)
cells that are unique to them which has a role in maintaining their stemness as
well as resistance towards harsh treatments and using these properties to
destroy CSCs and hence increasing the survival rates in patients as only the
complete eradication of CSCs will eliminate the possibility of relapse.

 

       According to National Cancer Registry Programme, breast
cancer is now the most common cancer in most cities in India, and 2nd
most common in the rural areas.  Breast cancer accounts for 25% to 32% of
all female cancers in all major cities of India. This implies, practically, one
fourth (or even approaching one thirds) of all female cancer cases are breast
cancers. Even after the surgery, chemo therapy and radiation, tumor reappears
after some years in majority cases. One of the reasons of this re-appearance is
the non-destructiion of cancer stem cells even after all the treatments
possible.

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      Cancer stem cells (CSCs) are defined as a
subpopulation of tumor cells with the capacity for self-renewal and
differentiation to drive the initiation, progression, metastasis and recurrence
of tumor. Studies have shown the existence of stem-like/progenitor cells in
several types of cancers including leukaemia, breast, brain, colon, liver and
melanoma. CSCs have resistance towards cancer treatments as well as the ability
to remain viable even after conventional chemo- and radio- therapies and to
establish the re-establishment of tumors. It will be a breakthrough if we can
destroy the CSCs completely, hence increasing the survival rate drastically. Studies
in this area have started already and people have even found that  anti-leukemia drug TDZD-8
selectively killed leukemia stem cells while not affecting normal hematopoietic
stem and progenitor cells. More people working on this area and the developing technologies
will make this destruction of CSCs soon.

       Experiments mainly
include In-vitro culturing of
breast Cancer stem cells isolated from tumor and identifying the genes which are
differentially expressed in them compared to other cancer cells and elucidating
their role in maintaining CSC’s potency as well as resistance towards harsh
treatment conditions. Using antagonists against this factors either at protein
level or mRNA level which possibly lead to the destruction of CSCs. And finally,
an extension of this method in-vivo. If a single factor which seems ultimately
necessary for CSCs maintenance is present, that can lead to a drug discovery.

Culture the cells
from tumor at breast. By taking advantage of the stem cell
ability to survive in suspension culture combined with slow proliferation rate,
we can isolate stem cells from normal human mammary gland based on retention of
a membrane-labeling dye, PKH26. (bsc3). Also, CSCs can be sorted by cell surface markers CD44 and CD24 and
ALDH1 protein. ALDH1+ CD44+/CD24-/low also
represents stem cell population in breast cancer. Sorting these cells can be
used to identify the genes which are either upregulated or downregulated in
those cells in comparison with other tumor cells. These can be candidate
factors responsible for their maintenance. Treating the drugs against these
candidate proteins in culture and see how the cell survival has affected. Drugs
that showed decreased survival rate can be used for in-vivo confirmational
studies.

For in-vivo studies,
induce tumor in immune-deficient mice. After the tumor has formed, a dose of
chemo drugs along with nanoparticles mediated drug delivery specific to CSCs
can be applied. Look for the relapse of tumor and confirm the drug efficiency.
Optimize the dosage and time for efficient drug treatment.