gemcitabine

Background : First-line therapy’s (tx) choice between the two most efficacious approved regimens (FOLFIRINOX and Gemcitabine plus Nab-Paclitaxel - GemNab) in mPDAC is usually based on patients’ (pts) baseline characteristics... HR-DDR somatic alterations emerged as possible predictor of lower benefit from platinum-free regimens. Thus, platinum-based regimens should be preferred in this setting. Validation in wider cohorts and correlation with HR-DDR germline mutations are warranted.

The data presented in this study are consistent with the results of TOPAZ1 trial. However about a third of patients do not respond to CHT or have a short response duration. In our experience both NLR and basal elevated AST/ALT seem to be associated with an improved mPFS and a better outcome but further studies are needed.

Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.

This report supports the clinical benefit of anti-EGFR antibodies for EGFR-amplified biliary tract cancers and the importance of genomic analysis in personalized therapy and drug resistance research.

Our findings suggest that the mutual validation of big data analysis and functional experiments may facilitate the precise identification and definition of biomarkers, and our m6A risk models may have the potential to guide personalized chemotherapy, targeted treatment, and immunotherapy decisions in HCC.

In the treatment of locally advanced NPC, a randomized phase III study showed equivalence of induction (ICT) and adjuvant therapy (AT; NCT03306121). PD-1 inhibitors have become established in the palliative therapy of NPC in recent years and could now also play an increasing role in curation: the phase III study "Dipper" showed a significantly better 3‑year event-free survival in patients adjuvantly treated with camrelizumab versus placebo after IT and definitive platinum-containing chemoradiotherapy (dRCT; 89% vs. 80%; NCT03427827). The phase III study "Beacon" showed complete remission in 30.5% of patients after IT with gemcitabine/cisplatin and the PD‑1 inhibitor tislelizumab (three cycles), a rate almost twice as high as with gemcitabine/cisplatin alone (NCT05211232). Intensification of dRCT in NPC using EGFR and VEGF inhibitors appears promising (NCT04447326). Abstracts on salivary gland and nasal and sinus cancers emphasize the importance of targeted therapies. In anaplastic thyroid carcinoma, the combination of a PD‑1 inhibitor and a CTLA4 inhibitor showed a 50% response.

We conclude that TGF-β is only one of the players that mediates the communication between PDAC cells and fibroblasts and controls the acquisition of aggressive phenotypes. Hence, these advanced in vitro models may be exploited to further investigate these events and to design innovative anti-PDAC therapies.

P1, N=353, Completed, Eli Lilly and Company | Active, not recruiting --> Completed

The combination of JQ1 + a pan CDC25 inhibitor was synergistic in gemcitabine-resistant Panc1.gemR cells that had relatively high levels of CDC25B expression compared to parent cells. The data suggest that CDC25B may be an independent indicator of sensitivity to BET inhibitors and that CDC25B may contribute to gemcitabine insensitivity in this tumor type.

P2, N=120, Recruiting, BeBetter Med Inc

P2, N=34, Recruiting, University of Florida | Not yet recruiting --> Recruiting

P2, N=0, Withdrawn, Georgetown University | N=28 --> 0 | Recruiting --> Withdrawn

P1, N=750, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

P1, N=1, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024

P3, N=68, Completed, Krankenhaus Nordwest | Recruiting --> Completed | N=300 --> 68

P4, N=132, Not yet recruiting, harbin medical university cancer hospital; harbin medical university cancer hospital

P2, N=20, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=61, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=72, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=54, Not yet recruiting, The second hospital of Lanzhou University; The second hospital of Lanzhou University

P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2026 --> Jan 2025 | Trial primary completion date: Oct 2025 --> Jan 2025

P3, N=595, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P2, N=13, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 13

P1/2, N=116, Recruiting, Cantargia AB | Trial primary completion date: Aug 2026 --> Jun 2025

P2, N=0, Withdrawn, Nicklaus Children's Hospital f/k/a Miami Children's Hospital | N=10 --> 0 | Active, not recruiting --> Withdrawn

P3, N=53, Active, not recruiting, Ferring Ventures Limited | Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Nov 2023 --> Mar 2024

Drug sensitivity analysis showed significantly higher IC50 values for 5-fluorouracil, gemcitabine, and sorafenib in patients with low MRTO4 expression than in those with high MRTO4 expression. MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with clinical stage, tumor grade, and drug sensitivity in HCC. It may serve as a putative therapeutic target and potential biomarker for prognosis of HCC.

There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

P2/3, N=130, Terminated, Tyme, Inc | Completed --> Terminated; Sponsor's decision

P2/3, N=685, Active, not recruiting, NRG Oncology | Phase classification: P3 --> P2/3

Our findings revealed the dual-functional significance of TPX2 in controlling DNA DSB repair pathway choice and mitotic progression, suggesting a potential therapeutic strategy involving PARPi for patients with pancreatic cancer.

P3, N=520, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2029 --> Jan 2027

P4, N=100, Recruiting, Coherus Biosciences, Inc. | Not yet recruiting --> Recruiting

P1, N=1, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=14, Active, not recruiting, Barts & The London NHS Trust | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2025 | Trial primary completion date: Jun 2021 --> Jun 2025

Systemic therapy, such as chemotherapy using gemcitabine and cisplatin, is the first choice for patients with cholangiocarcinoma who were inoperable. The development of precision medicine has expanded the paradigm of targeted therapies to increasingly favorable options in the second line and beyond, and prolong overall survival. Detecting druggable mutations (mutations potentially amenable to treatment with) for identifying a landscape of therapeutic options is imperative for managing cholangiocarcinoma.

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

The most frequent grade 3 or 4 treatment-related adverse event was neutropenia (n = 4, 29%). The combination of camrelizumab, gemcitabine, and apatinib showed promising efficacy and acceptable safety in patients with advanced PD-L1-positive biliary tract cancer.

P2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> May 2025 | Trial primary completion date: Jan 2025 --> May 2025

The combined application of the EP300 inhibitor inobrodib and gemcitabine exerts a synergistic effect on PDAC. Overall, these findings reveal that the EP300-CMTM6-IGF2BP1 positive feedback loop facilitates gemcitabine resistance via epigenetic reprogramming and the combined use of inobrodib and gemcitabine represents a promising strategy for overcoming chemoresistance in PDAC, warranting further investigation in clinical trials.

Compared to WT, tumor growth was attenuated in Pld1-/- mice by 39%, whereas treatment of Pld1-/- mice with gemcitabine reduced tumor growth by 79%...Mechanistically, the effect of PLD on tumor growth is mediated, partly, by the FAK pathway. In conclusion, while PLD1 is a critical regulator of pancreatic xenograft and allograft growth, playing an important role at the tumor and at the microenvironment levels, inhibition of PLD1 and PLD2 are necessary to reduce pancreatic carcinogenesis in KC mice, and might represent a novel therapeutic target.