Known as the "King of Cancers", pancreatic cancer is characterized by high malignancy, insidious early-stage manifestations, and extreme therapeutic difficulty. It has long had a 5-year survival rate of less than 10%, representing a formidable challenge in global oncology treatment.

With profound breakthroughs in basic research and intensive strategic deployment by innovative pharmaceutical companies, pancreatic cancer treatment is undergoing a transformative revolution. From the "undruggable" KRAS target to multiple targeted agents entering Phase III clinical trials, from the inefficacy of immunotherapy for "cold tumors" to long‑term survival achieved by bispecific antibodies and cell therapies, and from chemotherapy resistance to combination regimens overcoming drug resistance, every advance is rewriting the survival outlook for patients.

Source: Reference [1]

Key Breakthrough in Targeted Therapy: Conquering the KRAS "Curse" and Covering Major Mutant Subtypes

1.Spanish team eradicates pancreatic cancer in mice with triple combination therapy, solving drug resistance

A research group from the Spanish National Cancer Research Center published a landmark study in PNAS. Using a triple regimen combining a KRAS inhibitor, an EGFR inhibitor, and a STAT3 inhibitor, the team achieved marked tumor regression in PDAC mouse models with concurrent KRAS and TP53 mutations. Long-term recurrence-free survival was observed after drug withdrawal, with minimal side effects and no significant abnormalities in liver/kidney function or body weight.

The core breakthrough of this study lies in the simultaneous blockade of the upstream (EGFR), downstream, and compensatory escape pathways (STAT3) of the KRAS signaling cascade, which mechanistically reduces tumor drug resistance. This provides a novel paradigm for curative-intent therapy of human pancreatic cancer.

Source: Reference [2]

2.Chinese team establishes pancreatic cancer organoid biobank, unraveling mechanisms of chemotherapy resistanceThe research group led by Gao Dong at the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, in collaboration with multiple institutions, published findings in Cell. They established a pancreatic cancer organoid biobank encompassing a large number of PDAC samples, other histological subtypes, and normal pancreatic tissues. Through integrated multi-omics analysis, the team demonstrated for the first time that elevated protein glycosylation and aberrant cholesterol metabolism are core hallmarks of chemotherapy resistance in pancreatic cancer.Furthermore, the team identified that in chemotherapy-refractory patients, combination therapy with atorvastatin led to reduced tumor markers and tumor shrinkage in a subset of individuals, offering an innovative repurposing strategy of existing drugs for resistant patients.

Source: Reference [3]

3.Targeting the Tumor Stroma to Overcome Drug Delivery Barriers and Uncover Novel Mechanisms Underlying Epithelial-Mesenchymal Regulation

In research on cell-cell communication in the tumor microenvironment, Chinese scientific teams have achieved a major breakthrough. The team led by Zhang Changhua at the Seventh Affiliated Hospital of Sun Yat-sen University, in collaboration with the group led by Academician Axel Behrens of The Institute of Cancer Research (ICR) in the UK, published a landmark pancreatic cancer study in the top international journal Nature in September 2025. This work revealed, for the first time, the bidirectional regulatory crosstalk between epithelial and mesenchymal cells in pancreatic cancer.

Source: Reference [4]

Corporate Pipeline Layout: Expansion of Approved Drugs and Intensive Breakthroughs of Clinical-Stage New Drugs

(I)Approved Drugs: Precision Stratification as the Cornerstone of Standard Therapy

(II) New Drugs in Clinical Stage: Targeted, Immunological and Combination Therapies Flourish Across the Board, Significantly Improving Survival Outcomes

1.KRAS Targeted Agents: From "Single Target" to "Pan-Mutation", Covering 35%–95% of Patients

2. Immunotherapies and Bispecific Antibodies: Overcoming the "Cold Tumor" Dilemma, Doubling Efficacy in Combination with ChemotherapyCLDN18.2/CD47 bispecific antibody: In a Phase II trial combined with GnP chemotherapy, it achieved a DCR of over 90%, with a median OS significantly superior to chemotherapy alone. It is among the world’s most advanced CD47-targeted agents for solid tumors.TQB2868: Developed by Chia Tai Tianqing, a PD-1/TGF-β bispecific antibody. In combination with anlotinib plus AG chemotherapy, Phase II data demonstrated excellent anti-tumor activity, with ORR, DCR and PFS all outperforming conventional regimens. Phase III trial has been initiated, positioning it as a potential benchmark for integrated "immunotherapy + targeted therapy + chemotherapy" regimens.Surufatinib + Camrelizumab + AG regimen: Developed by Hutchison MediPharma. In a Phase II study, median PFS and ORR were significantly better than those with AG chemotherapy alone, with a marked reduction in the risk of disease progression. Phase III trial is ongoing.

3. Other Innovative Therapies: ADCs and Pan-Cancer Targeted Agents Expanding IndicationsTrastuzumab Deruxtecan (T-DXd): A HER2-targeted ADC. In Phase II studies, patients with HER2-high (IHC 3+) pancreatic cancer showed favorable improvements in ORR, PFS and OS, supporting its recommendation for HER2-positive pancreatic cancer.Larotrectinib: Developed by Bayer, an NTRK fusion inhibitor. It demonstrates significant efficacy in NTRK fusion-positive pancreatic cancer, offering a precise therapeutic option for patients with this rare mutation.

Reference

[1]Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health. 2018;6(5):e555-e567. doi:10.1016/S2214-109X(18)30127-X

[2]Liaki V, Barrambana S, Kostopoulou M, et al. A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance. Proc Natl Acad Sci U S A. 2025;122(49):e2523039122. doi:10.1073/pnas.2523039122

[3]Li Y, Tang S, Wang H, et al. A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy. Cell Stem Cell. 2025;32(9):1369-1389.e14. doi:10.1016/j.stem.2025.07.008

[4]Li H, Lan L, Chen H, et al. SPP1 is required for maintaining mesenchymal cell fate in pancreatic cancer. Nature. 2025;648(8092):203-209. doi:10.1038/s41586-025-09574-y