Gatekeeper Mutations and Intratumoral Heterogeneity in<i>FGFR2</i>-Translocated Cholangiocarcinoma

Smyth, Elizabeth; Babina, Irina S.; Turner, Nicholas C.

doi:10.1158/2159-8290.cd-17-0057

Cited by 12 publications
(11 citation statements)

References 11 publications

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“…FGFRs represent tyrosine kinase receptors, with FGFR2 being involved in the upregulation of RAS, JAK, and PI3K/mTOR pathways; thus, FGFR2 aberrations play a role in modifying processes of cellular migration, angiogenesis, proliferation, and survival [ 43 , 44 ]. In the last decade, a wide number of agents targeting FGFR isoforms have been investigated in iCCA patients, such as infigratinib, pemigatinib, derazantinib, erdafitinib and, more recently, futibatinib ( Table 1 ) [ 45 , 46 ].…”

Section: Targeted Therapiesmentioning
confidence: 99%

Systemic Treatment for Metastatic Biliary Tract Cancer: State of the Art and a Glimpse to the Future
Rizzo
¹
,
Ricci
²
,
Cusmai
³

et al. 2022
Current Oncology
6
0
1
0
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Recent years have seen some breakthroughs in the therapeutic landscape of advanced biliary tract cancer (BTC). Firstly, a better understanding of the molecular background of BTC has led to important improvements in the management of these hepatobiliary malignancies, with the advent of targeted agents representing an unprecedented paradigm shift, as witnessed by the FDA approval of pemigatinib and infigratinib for FGFR2-rearranged and ivosidenib in IDH1-mutant cholangiocarcinoma. In addition, several novel treatments are under assessment, including immune checkpoint inhibitors and combination chemotherapies. In the current review, we provide an overview of systemic treatment for metastatic BTC, summarizing recent clinical data on chemotherapy as well as the main results of targeted therapies and immunotherapy.

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Section: Targeted Therapiesmentioning
confidence: 99%

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“…The first evidence of FGFR2 fusions in iCCA patients was reported by Wu and colleagues in 2013 [ 53 ]; subsequently, an impressive number of studies have been published on this topic, also observing that etiology and geographical elements could modify the prevalence of FGFR aberrations in CCA. Recent years have registered the advent of several different methods able to identify FGFR2 fusions, including traditional immunohistochemistry, polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH), and other approaches based on NGS [ 56 ]. Nonetheless, these methods are not superimposable since they have been associated with considerable differences in terms of comparability, reproducibility and specificity.…”

Section: Fgfr Aberrations In Cholangiocarcinomamentioning
confidence: 99%

Targeted Therapies in Advanced Cholangiocarcinoma: A Focus on FGFR Inhibitors
Rizzo
¹

2021
Medicina
9
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7
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Despite advanced diseases continuing to be associated with grim prognoses, the past decade has witnessed the advent of several novel treatment options for cholangiocarcinoma (CCA) patients. In fact, CCA has emerged as a heterogeneous group of malignancies harboring potentially druggable mutations in approximately 50% of cases, and thus, molecularly targeted therapies have been actively explored in this setting. Among these, fibroblast growth factor receptor (FGFR) inhibitors have reported important results, as witnessed by the FDA approval of pemigatinib in previously treated metastatic CCA patients harboring FGFR2 fusion or other rearrangements. Herein, we provide an overview of available evidence on FGFR inhibitors in CCA, especially focusing on the development, pitfalls and challenges of emerging treatments in this setting.

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“… 50 Acquired resistance is often linked to tumor heterogeneity and the occurrence of secondary mutations in the FGFR2 kinase domain. 84 This phenomenon can be regarded as the stress response of cancer cells to therapeutic drugs. Recently, Krook et al reported a patient with metastatic cholangiocarcinoma and altered FGFR2 who was enrolled in a phase II clinical trial of the FGFR inhibitor BGJ398.…”

Section: Fgfr Targeted Therapy For Iccamentioning
confidence: 99%

Intrahepatic Cholangiocarcinoma: State of the Art of FGFR Inhibitors
Wu
¹
,
Jiang
²
,
Zhang
³

et al. 2021
Cancer Control
2
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2
0
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Objective: Intrahepatic cholangiocarcinoma (iCCA), the second most common type of primary liver tumor, has an increasing incidence in the past few decades. iCCA is highly malignant, with a 5-year survival rate of approximately 5-10%. Surgical resection is usually the prescribed treatment for patients with early stage iCCA; however, patients are usually in an advanced stage iCCA upon diagnosis. Currently, targeted therapy combined with chemotherapy and other comprehensive treatment measures have been mainly adopted as palliative treatment measures. As a common candidate of targeted therapy, FGFR inhibitors have demonstrated their unique advantages in clinical trials. At present, the prospect of FGFR targeted therapy is encouraging. The landscape of FGFR inhibitors in iCCA is needed to be showed urgently. Methods: We searched relative reports of clinical trials on FGFR inhibitors in PubMed as well as Web of Science. We also concluded other available clinical trials of FGFR inhibitors (Data were collected from clinicaltrials.gov ). Results: Several relatively effective targeted drugs are being used in clinical trials. Some preliminary results indicate the outlook of targeted therapy such as BGJ398, TAS120, and HSP90 inhibitors. Conclusions: In summary, FGFR targeted therapy has broad prospects for the treatment of iCCA.

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Gatekeeper Mutations and Intratumoral Heterogeneity inFGFR2-Translocated Cholangiocarcinoma

Cited by 12 publications

References 11 publications

Systemic Treatment for Metastatic Biliary Tract Cancer: State of the Art and a Glimpse to the Future

Systemic Treatment for Metastatic Biliary Tract Cancer: State of the Art and a Glimpse to the Future

Targeted Therapies in Advanced Cholangiocarcinoma: A Focus on FGFR Inhibitors

Intrahepatic Cholangiocarcinoma: State of the Art of FGFR Inhibitors

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