Identifying patients suitable for targeted adjuvant therapy: advances in the field of developing biomarkers for tumor recurrence following irradiation

ABSTRACT

Introduction

Radiation therapy (RT) is commonly used to treat cancer in conjunction with chemotherapy, immunotherapy, and targeted therapies. Despite the effectiveness of RT, tumor recurrence due to treatment resistance still lead to treatment failure. RT-specific biomarkers are currently lacking and remain challenging to investigate with existing data since, for many common malignancies, standard of care (SOC) paradigms involve the administration of RT in conjunction with other agents.

Areas Covered

Established clinically relevant biomarkers are used in surveillance, as prognostic indicators, and sometimes for treatment planning; however, the inability to intercept early recurrence or predict upfront resistance to treatment remains a significant challenge that limits the selection of patients for adjuvant therapy. We discuss attempts at intercepting early failure. We examine biomarkers that have made it into the clinic where they are used for treatment monitoring and management alteration, and novel biomarkers that lead the field with targeted adjuvant therapy seeking to harness these.

Expert Opinion

Given the growth of data correlating interventions with omic analysis toward identifying biomarkers of radiation resistance, more robust markers of recurrence that link to biology will increasingly be leveraged toward targeted adjuvant therapy to make a successful transition to the clinic in the coming years.

KEYWORDS:

• Radiation therapy (RT)
• adjuvant therapy
• biomarkers
• tumor recurrence
• radiation resistance
• precision medicine

Article highlights

• Optimization of tumor detection and progression due to treatment resistance is critical to identifying patients suitable for targeted adjuvant therapy.

• Imaging is the most reliable method for definitively detecting recurrence both while treatment is ongoing and after it is completed; however, there are practical constraints (cost and accessibility of frequent imaging) and the problem of distinguishing tumor progression from tissue and anatomical changes caused by treatment.

• Biomarkers analyzed in this review broadly fall under 4 categories: 1) established biomarkers employed for clinical decision-making; 2) established biomarkers used to detect recurrence; 3) evolving biomarkers of radiation resistance and 4) biomarkers of cancer stem cells.

• The current focus in developing adjuvant therapies involving RT focuses on optimizing early detection of recurrence, increasing radiation sensitivity often by targeting one of the known molecular features contributing to radiation resistance, and using machine learning to develop prognostic models that can help guide and select personalized radiation therapy.

• It is critical to focus on unraveling the molecular and genetic mechanisms that drive tumor growth and response to RT to refine and tailor existing treatment paradigms and identify novel targets for therapeutic intervention

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Cancer Institute, U.S. Department of Health and Human Services, National Institutes of Health Funding [ZID BC 010990].