Discussion and Conclusion:
Cancer cells employ a wide range of factors and mechanisms to resist
chemotherapy. Among these factors, the triad of CSCs, exosomes, and
ncRNAs are particularly prominent. CSCs not only utilize diverse
intracellular and extracellular mechanisms to develop chemoresistance
but also have a significant role in chemoresistance through their
interactions with various components of TME and other cancer cells.
Furthermore, It has also been established that CSCs play a crucial role
in recurrence after successful chemotherapy. As previously mentioned,
exosomes present in the microenvironment have a prominent role in
cellular communications and interactions between different components of
TME and cancer cells. Additionally, ncRNAs have an important role in
intracellular signaling pathways and intercellular communications
between CSCs and other factors. Therefore, it can be deduced that ncRNAs
are likely to have a significant impact on the function of mentioned
factors involved in chemotherapy resistance caused by CSCs. Moreover,
CSCs can utilize their high capacity of survival and chemoresistance to
stay alive after chemotherapy, as well as employ the combination of
exosomes and ncRNAs to spread chemoresistance among other cancerous
cells by establishing wide intercellular communications with tumor cells
and the tumor microenvironment components, ultimately leading to the
exacerbation of chemotherapy resistance and cancer relapse. Indeed,
ncRNA can be considered the most prominent factor among other factors in
the chemoresistance of CSCs. Therefore, an in-depth understanding of the
interactions between CSCs, exosomes, and ncRNAs is very important and
vital in achieving the desired chemotherapy results, and research in
these three fields is very necessary to understand their precise
function in chemotherapy resistance.
In addition, it is recommended that the use of smart nanoparticles as a
drug delivery method for small molecules could be an effective approach
for delivering a greater and more fruitful amount of small molecules to
cancer cells, considering the distinct conditions within the tumor
microenvironment (hypoxia, acidity, etc.). One of the challenges in drug
delivery is the limited understanding of drug targets.
Large-scale screening studies
using CRISPR-Cas technology can help to improve our understanding of
high-priority drug targets.
On the whole, the application of the following strategies can improve
the design and therapeutic outcomes of small molecule drugs as
combination therapy for chemotherapy:
1. Focusing more research on interactions between CSCs, exosomes, and
ncRNAs as well as their function in chemotherapy resistance for a better
and deeper understanding of these areas.
2. Identifying the factors that maintain proper function and favorable
interactions between CSCs, exosomes, and ncRNAs to be considered as
targets for small molecule drugs so that targeting them causes effective
disruption in the function and interactions of these three components.
3. Launching extensive screening studies using CRISPR-Cas technology to
identify potential drug targets for the design of effective small
molecule drugs.
4. More research on drug delivery systems based on smart nanoparticles
to improve and increase their efficiency in the appropriate and
sufficient delivery of small molecule drugs to the tumor
microenvironment and cancer cells.