Repurposing Proton Beam Therapy through Novel Insights into Tumour Radioresistance

Area of Science:

• Oncology
• Radiation Oncology
• Cancer Biology

Background:

• Radioresistance is a significant clinical challenge in radiotherapy, influenced by tumor DNA damage responses and the tumor microenvironment (TME).
• The TME's role, including hypoxia and wound healing, in radioresistance is increasingly recognized, yet combination therapies are limited by photon therapy's toxicity.
• Proton beam therapy (PBT) presents an advancement, but optimal clinical strategies and patient selection require further clarification.

Purpose of the Study:

• To explore the potential of PBT in overcoming radioresistance.
• To discuss how PBT can improve patient selection and toxicity profiles for combination therapies.
• To examine the role of FLASH PBT in addressing radioresistance through enhanced normal tissue sparing and direct mechanistic effects.

Main Methods:

• Review of current understanding of radioresistance mechanisms.
• Analysis of PBT's physical and biological advantages.
• Examination of FLASH PBT's unique properties and potential applications.

Main Results:

• PBT offers improved dose distribution and a potentially better toxicity profile compared to photon therapy.
• FLASH PBT demonstrates significant normal tissue-sparing effects.
• PBT and FLASH PBT can facilitate novel combination strategies to combat radioresistance.

Conclusions:

• PBT holds promise for improving patient selection and enabling combination treatments for radioresistant tumors.
• FLASH PBT's superior tissue-sparing capabilities may unlock new therapeutic combinations and directly address radioresistance mechanisms.
• Further research into PBT and FLASH PBT is crucial for optimizing their clinical application against radioresistance.