Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity.

Area of Science:

• Radiation oncology
• Cancer biology
• Molecular radiotherapy

Background:

• Proton radiotherapy is a standard cancer treatment, but its cellular mechanisms require further investigation.
• Cancer stem cell (CSC) biomarkers like aldehyde dehydrogenase (ALDH) impact radiosensitivity and treatment outcomes.
• Previous research indicated that ionizing radiation enriches ALDH-positive CSCs.

Purpose of the Study:

• To analyze CSC marker dynamics in prostate cancer, head and neck cancer, and glioblastoma cells following proton beam irradiation.
• To compare the effects of proton versus photon irradiation on CSCs.
• To investigate prognostic biomarkers for improved cancer therapy.

Main Methods:

• Irradiation of cancer cell lines (prostate, head and neck, glioblastoma) with proton and photon beams.
• Analysis of CSC marker dynamics, focusing on aldehyde dehydrogenase (ALDH) expression.
• Assessment of DNA damage, cellular senescence, and histone methylation patterns.
• Mathematical modeling of CSC plasticity rates.

Main Results:

• Proton irradiation demonstrated a higher potential to target CSCs compared to photon irradiation.
• Proton therapy induced more complex DNA damages and lower rates of cellular senescence.
• Proton irradiation caused minor alterations in histone methylation patterns relative to photon therapy.
• Mathematical modeling revealed distinct plasticity rates between ALDH-positive CSCs and ALDH-negative cells for both irradiation types.

Conclusions:

• Proton radiotherapy may offer superior targeting of CSCs due to its distinct biological effects.
• The findings suggest proton therapy could be a more effective strategy for eradicating CSCs, potentially improving patient prognosis.
• Further research into CSC marker dynamics and radiosensitivity is crucial for optimizing cancer treatment.