Publications

Despite the development of novel therapeutic regimens and drugs, the long-term survival of cancer patients is still very low, especially for those whose diagnosis is not caught early enough. Meanwhile, our understanding of tumorigenesis is still limited. Suitable research models are essential tools for exploring cancer mechanisms and treatments. Herein we review and compare several widely used in vitro and in vivo murine cancer models, including syngeneic tumor models, genetically engineered mouse models (GEMM), cell line-derived xenografts (CDX), patient-derived xenografts (PDX), conditionally reprogrammed (CR) cells, organoids, and MiniPDX. 

Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations.

Cancers affecting the gastrointestinal system are highly prevalent and their incidence is still increasing. Among them, gastric and pancreatic cancers have a dismal prognosis (survival of 5–20%) and are defined as difficult-to-treat cancers. This reflects the urge for novel therapeutic targets and aims for personalised therapies. As a prerequisite for identifying targets and test therapeutic interventions, the development of well-established, translational and reliable preclinical research models is instrumental.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare but aggressive disease. Immune checkpoint inhibitors (ICIs) have been an indispensable component for the management of advanced renal cell carcinoma, and stereotactic body radiotherapy (SBRT) has offered additional immunological effect boost for improving the treatment outcomes of the patients. This case report demonstrates the synergistic effect of ICIs and SBRT in HLRCC and the potential mechanism for the repeated SBRT-induced abscopal effect, supporting the application of SBRT to oligometastatic lesion during ICIs treatment to delay disease progression.

The PDX, PDO, and PDC models are optimal humanized models currently in cancer research, which can successfully simulate the human body and clinical practice. The universalization of patient-derived models will support basic cancer research and provide additional scientific evidence for novel and effective drug development. For eventual clinical application, they will also yield more precise and reliable treatments.

Copy number alterations (CNAs) are pivotal genetic events in triple-negative breast cancer (TNBC). Here, our integrated copy number and transcriptome analysis of 302 TNBC patients reveals that gene alpha-endosulfine (ENSA) exhibits recurrent amplification at the 1q21.3 region and is highly expressed in TNBC. 

Systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC.

Over the past few decades, subcutaneous or orthotopic cell-derived tumour xenograft models (CDX models) have been developed to simulate distinct tumours in patients. For the past several years, the patient-derived xenograft model (PDX model) has emerged as a promising tool for translational research. In this review, we summarize the methodology, advantages/disadvantages and applications of PDX models in hepatopancreatobiliary cancer research.

Pancreatic cancer (PC) is one of the most fatal and chemoresistant malignancies with a poor prognosis. The current therapeutic options for PC have not achieved satisfactory results due to drug resistance. Therefore, it is urgent to develop novel treatment strategies with enhanced efficacy. This study sought to investigate the anticancer effect of gemcitabine and XCT790, an estrogen-related receptor alpha (ERRα) inverse agonist, as monotherapies or in combination for the treatment of PC.

It is estimated that 35% of gastric cancer patients appear with synchronous distant metastases—the vast majority of patients presenting with metastatic hepatic disease. How to choose the most appropriate drugs or regimens is crucial to improve the prognosis of patients. OncoVee™-MiniPDX, which was used to select drugs to guide antitumor treatment, was promising to prolong survival and improve the response rate of patients with GCLM