# Advancing systemic therapy for biliary tract cancer: current strategies and emerging paradigms **Authors:** Khalil Choucair, Shadi Chamseddine, Asfar Azmi, Philip A. Philip PMC · DOI: 10.3389/fonc.2026.1769447 · Frontiers in Oncology · 2026-02-11 ## TL;DR This paper discusses recent advances in systemic therapies for biliary tract cancer, emphasizing personalized treatments based on genomic profiling. ## Contribution The paper highlights a paradigm shift in BTC treatment through novel therapies and genomic-based personalized approaches. ## Key findings - Advances in molecular biology have transformed the treatment of biliary tract cancer. - Personalized therapies based on genomic profiling have improved outcomes for advanced BTC patients. - Targeted treatments are now a major step forward in managing this aggressive malignancy. ## Abstract Most patients diagnosed with biliary tract cancer (BTC) present with advanced, often unresectable disease. Additionally, a significant proportion of those who undergo curative intent resection experience disease recurrence. The aggressive nature and poor prognosis of BTC underscore the urgent need for effective and safe systemic therapies. For many years, progress in the therapy of BTC was limited. However, advances in our understanding of the molecular biology of BTC created a paradigm shift in its treatment. Novel therapies, particularly personalized approaches based on genomic profiling and use of targeted treatments, have significantly transformed the management algorithm for advanced BTC. These advances represented a major step forward in improving outcomes for patients with this very challenging malignancy. ## Linked entities - **Diseases:** biliary tract cancer (MONDO:0003060) ## Full-text entities - **Genes:** ADA2 (adenosine deaminase 2) [NCBI Gene 51816] {aka ADGF, CECR1, IDGFL, PAN, SNEDS, VAIHS}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233] {aka AUTS9, DA11, DFNB97, HGFR, RCCP2, c-Met}, Braf (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 109880] {aka 9930012E13Rik, B-raf, Braf-2, Braf2, C230098H17, D6Ertd631e}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, ARID1A (AT-rich interaction domain 1A) [NCBI Gene 8289] {aka B120, BAF250, BAF250a, BM029, C1orf4, CSS2}, GGTLC4P (gamma-glutamyltransferase light chain 4 pseudogene) [NCBI Gene 729838] {aka GGT}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, FGFR2 (fibroblast growth factor receptor 2) [NCBI Gene 2263] {aka BBDS, BEK, BFR-1, CD332, CEK3, CFD1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, LY6K (lymphocyte antigen 6 family member K) [NCBI Gene 54742] {aka CT97, HSJ001348, URLC10, ly-6K}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, BAP1 (BRCA1 associated deubiquitinase 1) [NCBI Gene 8314] {aka HUCEP-13, KURIS, TPDS1, UBM2, UCHL2, UVM2}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD} - **Diseases:** microsatellite (MESH:D053842), MSI-H/dMMR (MESH:C536928), BTCs (MESH:D001661), gallstones (MESH:D042882), cancer (MESH:D009369), diarrhea (MESH:D003967), oncogenesis (MESH:D063646), CCA (MESH:D018281), GBC (MESH:D005706), nausea (MESH:D009325), vomiting (MESH:D014839), systemic disease (MESH:D034721), salmonella infections (MESH:D012480), extrahepatic disease (MESH:D001651), hematologic toxicity (MESH:D006402), neutropenia (MESH:D009503), mOS (MESH:D011475), cytotoxic (MESH:D064420), biliary tract, pancreatic, and other gastrointestinal cancers (MESH:D005770), mucositis (MESH:D052016), impaired renal function (MESH:D007674), MSI-H (MESH:D000848), hepatocellular carcinoma (MESH:D006528) - **Chemicals:** 2-HG (MESH:C019417), derazantinib (MESH:C000621805), Dostarlimab (MESH:C000719628), Toripalimab (MESH:C000656314), trastuzumab (MESH:D000068878), infigratinib (MESH:C568950), Binimetinib (MESH:C581313), cobimetinib (MESH:C574276), paclitaxel (MESH:D017239), Futibatinib (MESH:C000713257), Irinotecan (MESH:D000077146), Leucovorin (MESH:D002955), trametinib (MESH:C560077), atezolizumab (MESH:C000594389), pertuzumab (MESH:C485206), Cabozantinib (MESH:C558660), pralsetinib (MESH:C000655704), 5-FU (MESH:D005472), T-DM1 (MESH:D000080044), oxaliplatin (MESH:D000077150), neratinib (MESH:C487932), bevacizumab (MESH:D000068258), Ivosidenib (MESH:C000627630), lapatinib (MESH:D000077341), ipilimumab (MESH:D000074324), doxorubicin (MESH:D004317), Ado (MESH:C110027), Entrectinib (MESH:C000607349), mitomycin-C (MESH:D016685), GEMCIS (-), erdafitinib (MESH:C000604580), Cisplatin (MESH:D002945), pemetrexed (MESH:D000068437), FOLFOX (MESH:C410216), Pemigatinib (MESH:C000705477), Selpercatinib (MESH:C000656166), Zanidatamab (MESH:C000726995), capecitabine (MESH:D000069287), Pembrolizumab (MESH:C582435), Dabrafenib (MESH:C561627), niraparib (MESH:C545685), Camrelizumab (MESH:C000631724), Durvalumab (MESH:C000613593), FOLFIRINOX (MESH:C000627770), Liposomal (MESH:C050797), lenvatinib (MESH:C531958), tucatinib (MESH:C000705452), ATP (MESH:D000255), levofolinic acid (MESH:D058766), afatinib (MESH:D000077716), Larotrectinib (MESH:C000609083), tremelimumab (MESH:C520704), hydroxyurea (MESH:D006918), Nivolumab (MESH:D000077594), Gemcitabine (MESH:D000093542) - **Species:** Homo sapiens (human, species) [taxon 9606] - **Mutations:** BRAFV600E ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12932168/full.md ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932168/full.md ## References 173 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932168/full.md --- Source: https://tomesphere.com/paper/PMC12932168