Genomics in non-adenoid cystic group of salivary gland cancers: one or more druggable entities?

ABSTRACT

Introduction: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignant tumors arising from either major or minor salivary glands. Among SGCs patients, adenoid cystic carcinoma (ACC) is the most frequent histotype and its genetic aberrations are well known even though they are generally uncommon. Non-ACC subtypes are rarer and more heterogeneous than ACC from a histological and genomic point of view. In non-ACC, some altered molecular pathways [e.g. BRAF or RET mutations, Androgen Receptor (AR)] are potentially targetable with specific drugs.

Areas covered: A literature search was performed to summarize the main druggable genomic aberrations involving non-ACC SGCs. An overview of the genomics of non-ACC salivary gland malignancies is discussed. We describe the pattern of potentially targetable genomic alterations in non-ACC salivary gland malignancies according to their frequency rather than to the single non-ACC histotype.

Expert opinion/commentary: The genetic profiling through in-depth molecular analyses [e.g. Next-generation sequencing (NGS)] is advised in all patients affected by recurrent and/or metastatic non-ACC SGCs to find any potentially druggable target. Some histotypes may carry driving mutations that must be investigated and defined. For the rare cancers, access to a referral center is recommended to optimize the management of these patients.

KEYWORDS:

• Salivary gland cancer
• genomics
• druggable
• targeted therapy
• salivary duct carcinoma
• MASCC

Article Highlights

1. Non-adenoid cystic carcinomas (non-ACCs) are rarer and more heterogeneous than ACC as subtypes of salivary gland malignancies

2. Non-ACC have higher rates of genomic alterations than ACC

3. Some genomic alterations recurring in non-ACC are potentially druggable

4. In-depth molecular analyses are advised in patients with advanced non-ACC

5. Access to referral centers is recommended to optimize the management of non-ACC patients

This box summarizes key points contained in the article.

Declaration of interest

L Licitra has disclosed funding (to her institution) for clinical studies and research from AstraZeneca, Boehringer Ingelheim, Eisai, Merck Serono, MSD, Novartis, and Roche, has received compensation for service as a consultant/advisor and/or for lectures from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Eisai, Merck Serono, MSD, Novartis, Roche, and Sobi; and has received travel coverage for meetings from Bayer, Bristol-Myers Squibb, Debiopharm, Merck Serono, MSD, and Sobi. P Bossi has disclosed honoraria or consultation fees from Roche, Merck Serono, Mundipharma, Kyowa Kirin, AstraZeneca. LD Locati has disclosed honoraria or consultation fees from Eisai, IPSEN, Merck Serono, MSD, BMS. The authors have no other 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.