Experimental HER2- targeted therapies for biliary tract cancer

ABSTRACT

Introduction: Biliary tract cancers (BTCs) constitute a heterogeneous group of poor-prognosis solid tumors with limited treatment options. In the last decade, global efforts have tried to identify therapeutic targets by genomic profiling of BTC, unveiling several genetic aberrations that could play a prognostic and/or a predictive role in these malignancies.

Areas covered: In this review, we will present an overview regarding the role of HER2 targeted therapies in BTC, with a particular focus on clinical studies carried out in this field to date and ongoing trials. A literature search was conducted in August 2020 of Pubmed/Medline, Cochrane library and Scopus databases for published preclinical and clinical studies; moreover, abstract of international cancer meetings (AACR, ASCO, and ESMO) were reviewed.

Expert opinion: Despite recent advances in medical oncology, the overall survival of BTC patients remains low and there is an urgent need for novel and more effective treatments. Although HER2 blockade has been suggested to induce durable tumor responses in selected subjects with BTC, controversial results have been reported so far and data from ongoing prospective clinical trials are awaited to further clarify the role of anti-HER2 therapies in BTC.

KEYWORDS:

• HER2
• targeted therapies
• biliary tract cancer
• cholangiocarcinoma
• gallbladder cancer

Article highlights

• Biliary tract cancers (BTCs) are a heterogeneous group of hepatobiliary malignancies with limited treatment options and poor survival

• Despite global efforts have been focused on genomic profiling of BTC, Precision Medicine Era in BTC is limited to intrahepatic cholangiocarcinoma so far

• Among experimental treatments currently under evaluation, the human epidermal growth factor receptor (HER)2-directed agents are being tested, with a view to translate the experience of breast cancer and gastric adenocarcinoma in BTC

• To date, although preclinical studies have shown promising data, HER2 targeted therapies have shown controversial results in metastatic BTC

• Prospective clinical trials are awaited in order to clarify the role of HER2 targeted treatment in advanced BTC

Disclosure statement

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 relationships or otherwise to disclose.

Additional information

Funding

This research received no financial support.