Ionizing Radiation Exposure and Basal Cell Carcinoma Pathogenesis

Abstract

This commentary summarizes studies showing risk of basal cell carcinoma (BCC) development in relationship to environmental, occupational and therapeutic exposure to ionizing radiation (IR). BCC, the most common type of human cancer, is driven by the aberrant activation of hedgehog (Hh) signaling. Ptch, a tumor suppressor gene of Hh signaling pathway, and Smoothened play a key role in the development of radiation-induced BCCs in animal models. Epidemiological studies provide evidence that humans exposed to radiation as observed among the long-term, large scale cohorts of atomic bomb survivors, bone marrow transplant recipients, patients with tinea capitis and radiologic workers enhances risk of BCCs. Overall, this risk is higher in Caucasians than other races. People who were exposed early in life develop more BCCs. The enhanced IR correlation with BCC and not other common cutaneous malignancies is intriguing. The mechanism underlying these observations remains undefined. Understanding interactions between radiation-induced signaling pathways and those which drive BCC development may be important in unraveling the mechanism associated with this enhanced risk. Recent studies showed that Vismodegib, a Smoothened inhibitor, is effective in treating radiation-induced BCCs in humans, suggesting that common strategies are required for the intervention of BCCs development irrespective of their etiology.

SMC1A is associated with radioresistance in prostate cancer and acts by regulating epithelial‐mesenchymal transition and cancer stem‐like properties

“…Radiation therapy remains an important modality for primary as well as locally advanced prostate cancer patients . However, radio‐resistance and relapse/recurrence of tumor remains a major clinical challenge . Therefore, it is critical to identify tumor‐specific targets and explore their linked signaling pathways associated with radioresistance.…”

“…Radiation therapy remains an important modality for primary as well as locally advanced prostate cancer patients. [7][8][9][10][11][12][13] However, radioresistance and relapse/recurrence of tumor remains a major clinical [8][9][10] Therefore, it is critical to identify tumor-specific targets and explore their linked signaling pathways associated with radioresistance. Emerging evidence suggests that aberrant activation of DNA-damage repair (DDR) signaling pathways play important roles in prostate cancer metastasis and progression and are involved in radio-resistance.…”

“…Currently available treatment options include administration of androgen receptor inhibitor (enzalutamide, abiraterone), cell cycle disruption (docetaxel, cabazitaxel), immune checkpoint‐related therapy (sipuleucel‐T), targeting of bone metastasis (radium‐223), and radiotherapy . Radiation therapy (RT) is widely considered a standard care treatment for primary and metastatic prostate cancer and is associated with high cancer control rates, although up to one‐third of patients receiving this therapy becomes radio‐resistant or manifest tumor‐recurrence . Radiotherapy kills the cancer cells directly by causing DNA damage, but radiation also causes the generation of reactive oxygen species (ROS) which are indirectly involved in DNA damage .…”

“…[4][5][6][7][8] Radiation therapy (RT) is widely considered a standard care treatment for primary and metastatic prostate cancer and is associated with high cancer control rates, although up to onethird of patients receiving this therapy becomes radio-resistant or manifest tumor-recurrence. [8][9][10] Radiotherapy kills the cancer cells directly by causing DNA damage, but radiation also causes the generation of reactive oxygen species (ROS) which are indirectly involved in DNA damage. [11][12][13] Moreover, RT promotes metastasis and invasion of cancer cells and is involved in epithelial-mesenchymal transition (EMT).…”

Double whammy: a tale of two malignancies

“…An increased risk has been noted with younger age of exposure; more severe radiodermatitis was associated with a higher prevalence of skin cancers. BCCs developing in irradiated skin tend to be more aggressive and have an increased propensity for recurrence 2. There is a pronounced rate of additional skin cancers once the first BCC has occurred.…”