Immunotherapy in Biliary Tract Cancers: Current Standard-of-Care and Emerging Strategies

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3312 - 3312

Published: June 23, 2023

Biliary tract cancers (BTCs), comprising intrahepatic, perihilar, and distal cholangiocarcinoma as well gallbladder adenocarcinoma, continue to be challenging manage. Conventional chemotherapy regimens for advanced disease are limited in both options benefits, more effective perioperative also needed. Over the last decade, immunotherapy has had a profound impact on management of many solid tumor types, particularly using immune checkpoint inhibition enable tumor-directed T cell response. Immunotherapy administered its own utility BTCs, part due hostile microenvironment relative infrequency biomarker-based tumor-agnostic indications immunotherapy. However, conjunction with chemotherapy, molecularly targeted therapies, and/or anti-angiogenic therapies gained traction, supported by evidence that these agents can impart favorable immunomodulatory effects microenvironment. The TOPAZ-1 trial led first BTC-specific approval, establishing combination durvalumab gemcitabine cisplatin preferred first-line treatment or metastatic disease. Recently, KEYNOTE-966 showed positive results pembrolizumab same setting, adding further addition standard backbone. Meanwhile, advances molecular profiling BTCs contributed recent proliferation therapeutics subset harboring alterations

Language: Английский

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Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 14, 2023

Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping multiple cohorts patients. We show that learning can reproduce the diagnosis HCC vs. CCA with high performance. analyze series 405 cHCC-CCA patients demonstrate model reclassify tumors as ICCA, predictions are consistent clinical outcomes, genetic alterations situ spatial gene expression profiling. This type approach could improve treatment decisions ultimately outcome for rare biphenotypic cancers such cHCC-CCA.

Language: Английский

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New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1244 - 1244

Published: Feb. 15, 2023

Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence on the rise, and despite important advances in knowledge molecular mechanisms, diagnosis, treatment, overall survival has not substantially improved last decade. Surgical resection remains cornerstone therapy for CCA. Unfortunately, complete only possible less than 15-35% cases, risk recurrence greater 60%. Liver transplantation (LT) been postulated as an effective therapeutic strategy those intrahepatic CCA (iCCA) smaller 3 cm. However, low rate early diagnosis non-resectable patients justifies applicability clinical practice. The evidence regarding LT locally advanced iCCA scarce based small, retrospective, and, most single-center case series. In this setting, response to neoadjuvant chemotherapy could be useful identifying subgroup biologically aggressive tumors whom may successful. results pCCA are promising, however, we need very careful selection adequate experience transplant center. Locoregional therapies relevant unresectable, liver-only 2 cm, particularly arising chronic disease or feasible, thermal ablation become reliable alternative. greatest management occur systemic treatment. Immunotherapy associated emerged gold standard first-line Likewise, encouraging have obtained targeted therapies, where use personalized treatments shown rates objective durable tumor response, clear signs benefit. conclusion, future treatment seems marked by development new strategies but high-quality, prospective studies shed light their mandatory.

Language: Английский

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Targetable Molecular Alterations in the Treatment of Biliary Tract Cancers: An Overview of the Available Treatments

Cancers, Journal Year: 2023, Volume and Issue: 15(18), P. 4446 - 4446

Published: Sept. 6, 2023

Biliary tract cancers (BTCs) are rare tumours, most often diagnosed at an unresectable stage, associated with poor prognosis, a 5-year survival rate not exceeding 10%. Only first- and second-line treatments well codified the combination of cisplatin-gemcitabine chemotherapy immunotherapy followed by 5-FU oxaliplatin chemotherapy, respectively. Many studies have shown that BTC, more particularly intrahepatic cholangiocarcinoma (iCCA), high targetable somatic alteration. To date, FDA has approved several drugs. Ivosidenib targeting IDH1 mutations, as futibatinib pemigatinib FGFR2 fusions, for pre-treated advanced CCA. The dabrafenib trametinib BRAFV600E mutated NTRK inhibitors entrectinib larotrectinib tumours bearing fusion prembrolizumab MSI-H involving small percentage BTC in these three settings. Several other potentially alterations found such HER2 mutations or amplifications KRASG12C genes involved DNA repair mechanisms. This review aims to clarify specific diagnostic modalities gene summarize results main trials developments underway management alterations.

Language: Английский

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Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types

Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 30(4), P. 836 - 848

Published: Dec. 7, 2023

Abstract Purpose: Genomic rearrangements can generate potent oncogenic drivers or disrupt tumor suppressor genes. This study examines the landscape of fusions and detected by liquid biopsy (LBx) circulating DNA (ctDNA) across different cancer types. Experimental Design: LBx from 53,842 patients with 66 solid types were profiled using FoundationOneLiquid CDx, a hybrid-capture sequencing platform that queries 324 cancer-related Tissue biopsies (TBx) FoundationOneCDx used as comparator. Results: Among all LBx, 7,377 (14%) had ≥1 pathogenic rearrangement detected. A total 3,648 (6.8%) gain-of-function (GOF) oncogene rearrangement, 4,428 (8.2%) loss-of-function Cancer higher prevalence GOF included those canonical fusion drivers: prostate (19%), cholangiocarcinoma (6.4%), bladder (5.5%), non–small cell lung (4.4%). Although driver was lower in than TBx overall, frequency detection comparable fraction (TF) ≥1%. Rearrangements FGFR2, BRAF, RET, ALK, types, but tended to be clonal variants some potential acquired resistance others. Conclusions: In contrast prior literature, this reports wide variety ctDNA. The tissue when TF presents viable alternative is not available, there may less value confirmatory testing sufficient.

Language: Английский

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