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Xu et al. Radiation therapy in keloids treatment

cell proliferation and apoptosis of human hypertrophic while cancer cells radiation therapy resistance is
scar fibroblasts through affecting collagen I and III, largely thought dependent on hypoxia. [96-98]
fibronectin expression and TGF-β1/α-SMA signaling. [88]
On the contrary, miR-200c overexpression could CONCLUSION
sensitize human breast cancer cells through escalation
of apoptosis and DNA double-strand breaks. Another We are still far away from generating a comprehensive
phenomenon is that overexpression of TBK1 can understanding of the underlying mechanisms
partially rescue apoptosis induced by miR200c. We in radiation therapy for keloid. Lack of detailed
predict that miR-200b could demonstrate similar effect fundamental studies also prevented us from
on keloid tissue radiosensitization. Along by more and uncovering the precise differences between radiation
more microRNAs identified being related to keloid therapy treating keloids or cancer cells. However,
formation or cellular response to radiation therapy, relatively lower genome instability and lower growth
these microRNAs will be candidates for therapeutic rate possibly indicate that the direct effect might
targets in radio-sensitization. [89] outweigh the indirect effect in killing keloid fibroblasts.
Cellular response to irradiation also varies between
Similarity and distinction to cancer cell, and keloids fibroblasts and cancer cells, ascribing to
its response to radiation comparatively intact DNA repair system. Some genes
Regarded as a benign tumor, keloids demonstrate which were thought to have the potential to drive keloid
formation and differentially expressed prior or post
some similarities of malignant tumors. Aberrant cell irradiation should be regarded as therapeutic targets.
growth pattern, indefinite proliferation, increased Furthermore, updating study of pathogenesis of keloids
proliferation rate and familial tendency enabled the including microRNA dysregulation and epigenetics
application of radiation therapy in disposing this might provide us with more potential in exploring
frustrating clinical problem. Compared to cancer cells, the keloids cells’ targets of radiation therapy. [99]
benign growth pattern of keloids do not exhibit the Currently, there are biological and antineoplastic agents
strong invasiveness and strong capacity of distant that can potentially treat and prevent excessive scar
metastasis. And molecular mechanisms varied largely formation. [100] However, prevention is the best way to
between keloid and malignant tumors. Specifically avoid the development of cosmetically unacceptable
narrowing down to keloid fibroblast response to ionizing scars. Clinically, although numerous treatments exist, no
irradiation, multiple genetic interrelated pathways single modality has been proven superior over others. [101]
were identified from different resources, like whole- Evidence in pediatric patients indicates that Asian patients
genome sequence or some inherited familial pattern have a three-fold increased rate of hypertrophic scarring
discovered. [90] Apoptotic and senescent cells were relative to Caucasians. [102] According to the guideline
identified from X-ray irradiation keloid tissues based update on scar management for treating Asian patients,
on extended G0/G1 phase and overexpression of it is recommended that all Asian patients should initiate
p16, p21 and p27, which were all senescence-related scar prevention following surgery. [103] Figuring out the
genes. [91] IL-6, as one of interleukins functioning in molecular mechanism of keloid could eventually help the
induced inflammations, was firstly identified based clinicians to better treat their patients, especially among
on bioinformatics analysis of post-irradiation keloid the Asian population. Understanding the molecular
fibroblasts global gene expression, [92] which seldom pathway in how to decrease profibrotic isoform could be
reports in other malignant tumors response towards crucial in accomplishing control of the fibrotic process
irradiation. Further evidence supporting this hypothesis underlying keloids. Comprehension of the molecular
ensued. IL-6 was then reported playing a critical mechanisms could lead to the development of new
role in benign tumor-like stem cell similar to keloid promising therapies for keloids.
derived precursor cells, suggesting inducing stem
cell associated gene overexpression, then indirectly Authors’ contributions
uncontrolled self-renewal and increased proliferation. [93]
The updating concept of keloid progenitor cells, Conception and design of the study: X. Long
exhibit clonogenicity, self-renewal, distinct embryonic Literature search and analysis : J. Xu
and mesenchymal stem cell surface markers, and Drafting the article: J. Xu, E. Yang, N.Z. Yu, Y.B. Wang
multipotent differentiation, indicating similar resistance
derived from cancer stem cells. [94] Furthermore, Financial support and sponsorship
in contrast to cancer cells, keloid cells displayed None.
enhanced apoptosis ratio in response to hypoxia,
which was thought as the key initiator enabling radio- Conflicts of interest
resistance through HIF-1 and VEGF dysregulation, [95] There are no conflicts of interest.
Plastic and Aesthetic Research ¦ Volume 4 ¦ July 28, 2017 123