Emerging role of precision medicine in biliary tract cancers

Abstract

Biliary tracts cancers (BTCs) are a diverse group of aggressive malignancies with an overall poor prognosis. Genomic characterization has uncovered many putative clinically actionable aberrations that can also facilitate the prognostication of patients. As such, comprehensive genomic profiling is playing a growing role in the clinical management of BTCs. Currently however, there is only one precision medicine approved by the US Food and Drug Administration (FDA) for the treatment of BTCs. Herein, we highlight the prevalence and prognostic, diagnostic, and predictive significance of recurrent mutations and other genomic aberrations with current clinical implications or emerging relevance to clinical practice. Some ongoing clinical trials, as well as future areas of exploration for precision oncology in BTCs are highlighted.

Comprehensive genomic landscape and precision therapeutic approach in biliary tract cancers

“…These findings also suggest the potential for precision clinical trials in biliary tract cancers, as well as that customized molecular targeting based on each individual genomic portfolio may be necessary to improve outcomes. 8,[28][29][30] Overall concordance between ctDNA and tissue-DNA was 68% to 90% for TP53, KRAS and PIK3CA genes. Discrepancies between the two tests may be due to the intertumor and intratumor genetic heterogeneity.…”

Circulating Tumor DNA in Biliary Tract Cancer: Current Evidence and Future Perspectives

“…A plethora of previous studies on BTC have grouped together patients with different anatomical and molecular subtypes, something which represents the "original sin" of several clinical trials which do not do justice to the marked inter-and intra-tumoral heterogeneity of BTC (67-69). The modest survival benefit observed with current treatment options emphasizes the need for new affective agents and tailor-made trials based on genetic profile and histological features characterizing BTC (70). The emergence of targeted treatments in BTC is challenging previous treatment paradigms, especially for iCCA for whom targeting FGFR fusions and IDH1/IDH2 mutations is becoming part of current clinical practice (71)(72)(73).…”

Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer

“…To date, the first-line treatment for patients with advanced BTC is a gemcitabine/cisplatin combination, of which clinical outcome is limited [2,3]. Given the huge unmet medical needs, potential targeted agents should be thoroughly developed in BTC.…”