Shedding light on emerging therapeutic targets for chordoma

ABSTRACT

Introduction

Despite encouraging advances in radiation and surgical treatment, chordomas remain resistant to chemotherapy and local recurrence is common. Although the primary mechanism of recurrence is local, metastatic disease occurs in a small subset of patients. Recurrence may also occur along the surgical trajectory if care is not taken to fully excise the open biopsy pathway. There is increasing morbidity with reoperation upon disease recurrence, and radiation is an option for cytoreduction in primary disease or for recurrent disease, although toxicity may be observed with high-dose therapies. Given these challenges, targeted chemotherapeutic agents for postoperative adjuvant treatment are needed.

Areas covered

In this review, we summarize the genetic drivers of chordoma and the state of the current research in chordoma immunotherapy and epigenetics.

Expert opinion

Chordoma is a heterogenous tumor that should be targeted from different angles and the study of its characteristics, from molecular to immunological to epigenetic, is necessary. Combining different approaches, such as studying noninvasive patient methylation patterns with tissue-based molecular and drug screening, can transform patient care by guiding treatment decisions based on prognostic mechanisms from different sources, while helping individualize surgical planning and treatment.

KEYWORDS:

• Chordoma
• tumor
• spine
• epigenetics

Article highlights

• Chordoma is driven by a variety of genetic and epigenetic mechanisms

• Targeted molecular therapies for chordoma will likely require combinatorial treatments, including tyrosine kinase inhibitors coupled with immune checkpoint inhibitors

• The tumor microenvironment plays a role in chordomagenesis

• It is unknown how clival and sacral chordoma differ in their genetic drivers, and future research is needed

Declaration of interests

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 materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.