CHEMOTHERAPY
AND CANCER CELLS - SCI & TECH
News: How do some cancer cells survive
chemotherapy? Scientists find one way
What's
in the news?
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Researchers at the Netherlands Cancer
Institute have conducted a recent study to investigate drug resistance in
cancer cells, focusing on resistance to a drug known as Taxol.
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It studied Chemotherapy and cancer
relapse, particularly when a small number of cancer cells resist treatment and
remain dormant, potentially leading to a resurgence of the disease.
Chemotherapy
and its limitations:
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Cancer
cells are characterized by uncontrolled and rapid division.
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Chemotherapeutic drugs aim to halt this
proliferation, often triggering programmed cell death, known as apoptosis, in response to halted cell
division.
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However, this approach also damages
healthy dividing cells, leading to adverse side effects.
Fine-Tuning
Cancer Treatment:
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Oncologists face the challenge of finding
an effective drug dose that eliminates cancer cells while minimizing unbearable
side effects for patients.
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One approach has been the development of antibody-drug conjugates
(ADCs) that target specific proteins found mainly on cancer cells, sparing
non-cancerous cells.
Unraveling
Drug Resistance:
1.
P-gp Protein:
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Some cancer cells escape drug treatments
by overexpressing a protein called P-gp (permeability glycoprotein), which acts
as a pump, expelling toxic compounds, including chemotherapeutic agents.
2.
ABCB1 Gene:
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The production
of P-gp is controlled by the ABCB1 gene and cells that produce excessive
P-gp can flush out chemotherapy drugs, preventing them from accumulating at
levels needed to trigger apoptosis.
Role
of Cellular Location:
1.
Recent Findings:
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The study examined the sensitivity of
cells to Taxol and identified that the location of the ABCB1 gene within the
cell’s nucleus plays a crucial role.
2.
Nuclear Envelope:
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In sensitive cells, the ABCB1 gene is
located close to the nuclear envelope. In resistant cells, the gene has
detached from the envelope and moved further inside the nucleus, resulting in a
100-fold increase in ABCB1 gene-related RNA.
3.
Key Protein - Lamin B Receptor (LBR):
●
LBR’s
Influence - Researchers discovered that the presence or absence of a protein called
Lamin B Receptor (LBR) affects the location of the ABCB1 gene.
●
Depletion
of LBR - When LBR is depleted, cells can activate the ABCB1
gene when exposed to Taxol. However, the absence of the LBR gene itself does
not immediately increase ABCB1 expression, indicating the involvement of
additional factors.
●
Diverse
Responses - Different cancer types exhibit varying responses to
LBR depletion, highlighting the complex mechanisms governing gene expression
and silencing.
Significance:
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These findings emphasize the need for
further research into the diverse ways cancer cells express or suppress genes.
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Understanding drug resistance mechanisms
opens avenues for developing strategies to maintain the potency of anti-cancer
drugs while minimizing side effects, ultimately benefiting patients on their
path to recovery.