Targets for therapy in biliary tract cancers: the new horizon of  personalized medicine

Iyer, Pritish; Chen, Ming-Huang; Goyal, Lipika; Denlinger, Crystal S.

doi:10.21037/cco.2019.12.11

Cited by 6 publications

(3 citation statements)

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“…The RAS-RAF-MEK-ERK, or mitogen-activated protein kinase (MAPK), pathway is involved in crucial processes of cell proliferation and survival. 45,46 Since BRAF is a member of these kinases, BRAF mutations-which have been found in several malignancies, including melanoma, non-small cell lung cancer and colorectal cancer-constitutively activate this pathway. [47][48][49][50] To date, more than 50 BRAF mutations have been described, the most common of which is the V600E point mutation.…”

Section: Braf Mutations In Biliary Tract Cancermentioning

confidence: 99%

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

et al. 2020

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Background: Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA). Methods & Results: In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials. Conclusions: Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade. In this discouraging scenario, BRAF inhibition is currently emerging as a novel treatment option in patients harboring BRAF mutations.

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Section: Braf Mutations In Biliary Tract Cancermentioning

confidence: 99%

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

et al. 2020

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“…The mitogen-activated protein kinase (MAPK) pathway is involved in the crucial cellular processes of proliferation and survival [ 42 ]. BRAF is a serine/threonine protein kinase representing an oncogenic driver in many human cancers [ 43 ].…”

Section: Inhibition Of Braf Pv600e In Ccamentioning

confidence: 99%

Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology

Capuozzo

Santorsola

Landi³

et al. 2022

IJMS

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Cholangiocarcinoma (CCA) is a malignant neoplasm arising in the epithelium of the biliary tract. It represents the second most common primary liver cancer in the world, after hepatocellular carcinoma, and it constitutes 10–15% of hepatobiliary neoplasms and 3% of all gastrointestinal tumors. As in other types of cancers, recent studies have revealed genetic alterations underlying the establishment and progression of CCA. The most frequently involved genes are APC, ARID1A, AXIN1, BAP1, EGFR, FGFRs, IDH1/2, RAS, SMAD4, and TP53. Actionable targets include alterations of FGFRs, IDH1/2, BRAF, NTRK, and HER2. “Precision oncology” is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from “old” chemotherapies to “new” target-oriented drugs.

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“…Strong activators of this pathway are BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, the most common of which is BRAF V600E (95). With regard to BTC, BRAF mutations are more frequent in iCCA compared with eCCA or GBC (96); more specifically, BRAF mutations have been reported in 1 to 22% of iCCAs in various population studies or cases series (96).…”

Section: Raf Mekmentioning

confidence: 99%

Second-line Treatment in Advanced Biliary Tract Cancer: Today and Tomorrow

et al. 2020

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Biliary tract cancer (BTC) patients usually have poor prognosis. Whereas combination chemotherapy has been shown to improve survival in the frontline setting, second-line treatment is subject to a lot of debate in the scientific community. Recent data of the ABC-06 trial has provided slight evidence for the use of second-line chemotherapy after progression on cisplatin plus gemcitabine combination. In this study, mFOLFOX plus active symptom control (ASC) improved overall survival (OS) after progression on cisplatingemcitabine combination compared with ASC alone, with an increase in 6-and 12-month OS rate. Although genomic studies have paved the way for a new age in cancer management, the "Precision Medicine Era" in BTC is still limited to intrahepatic cholangiocarcinoma and primarily focused on isocitrate dehydrogenase (IDH) and fibroblast growth factor receptor (FGFR) targeted therapies. We herein review recent published data regarding the use of second-line treatment after failure of standard first-line therapies in BTC patients, with a particular focus on ongoing active and recruiting clinical trials.

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Targets for therapy in biliary tract cancers: the new horizon of personalized medicine

Cited by 6 publications

References 0 publications

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology

Second-line Treatment in Advanced Biliary Tract Cancer: Today and Tomorrow

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