About

Chengfei Liu, M.D., Ph.D., is an Associate Professor in the Department of Urologic Surgery and the Assistant Director for Translational Research at UC Davis Comprehensive Cancer Center. He has extensive expertise in clinical oncology and prostate cancer research, with a focus on identifying novel resistance mechanisms and developing innovative pharmaceutical strategies to treat patients with advanced prostate cancer. His research has generated unique tools that elucidate how resistance emerges in late-stage disease. Dr. Liu’s long-term research interest is to bridge basic and clinical research to drive novel translational efforts in urologic oncology, aiming to establish new paradigms in protein post-translational modification and drug resistance in cancer cells, advance understanding of cancer biology, and provide opportunities for innovative cancer therapeutics. His current research program concentrates on uncovering mechanisms of therapy resistance and disease progression in lethal prostate cancer, with particular emphasis on drug development. His areas of interest include nuclear receptors, chaperone protein modification, ubiquitin-proteasome regulation, steroid hormone biosynthesis and metabolism, clinical translational research, and tumor immunology.

Research topics

• Internal medicine
• Medicine
• Cancer research
• Oncology
• Biology
• Pharmacology
• Endocrinology
• Cell biology
• Urology
• Biochemistry

Selected publications

• Steroid Sulfatase Regulates Metabolic Reprogramming in Advanced Prostate Cancer

  Cancers · 2025-06-12 · 1 citations

  articleOpen access

  BACKGROUND/OBJECTIVE: The expression of human steroid sulfatase (STS) is upregulated in castration-resistant prostate cancer (CRPC) and is associated with resistance to anti-androgen drugs, such as enzalutamide (Enza) and abiraterone (Abi). Despite the known link between STS overexpression and therapeutic unresponsiveness, the mechanism by which STS confers this phenotype remains incompletely understood. In this study, we sought to understand how STS induces treatment resistance in advanced prostate cancer (PCa) cells by exploring its role in altering mitochondrial activity. METHODS: To examine the effects of increased STS expression on mitochondrial respiration and programming, we performed RNA sequencing (RNA-seq) analysis, the Seahorse XF Mito Stress Test, and a mitochondrial Complex I enzyme activity assay in STS-overexpressing cells (C4-2B STS) and in enzalutamide-resistant CPRC cells (C4-2B MDVR). We employed SI-2, the specific chemical inhibitor of STS, on C4-2B STS and C4-2B MDVR cells and evaluated STS activity inhibition on mitochondrial molecular pathways and mitochondrial respiration. Lastly, we examined the effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on C4-2B STS organoids. RESULTS: We present evidence from the transcriptomic profiling of C4-2B STS cells that there are enriched metabolic pathway signatures involved in oxidative phosphorylation, the electron transport chain, and mitochondrial organization. Moreover, upon STS inhibition, signaling in the electron transport chain and mitochondrial organization pathways is markedly attenuated. Findings from the Seahorse XF Mito Stress Test and mitochondrial Complex I enzyme activity assay demonstrate that STS overexpression increases mitochondrial respiration, whereas the inhibition of STS by SI-2 significantly reduces the oxygen consumption rate (OCR) and Complex I enzyme activity in C4-2B STS cells. Similarly, an increased OCR and electron transport chain Complex I enzymatic activity are observed in C4-2B MDVR cells and a decreased OCR upon SI-2 inhibition. Lastly, we show that STS overexpression promotes organoid growth upon DHEAS treatment. CONCLUSIONS: Our study demonstrates STS as a key driver of metabolic reprogramming and flexibility in advanced prostate cancer. Disrupting enhanced mitochondrial respiration via STS presents a promising strategy in improving CRPC treatment.

  PublisherOA PDFDOI

• Figure S2 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2025-04-03

  preprintOpen access

  <p>supplementary data</p>

  PublisherDOI

• Development and validation of a risk prediction model related to inflammatory and nutritional indexes for postoperative pulmonary infection after radical colorectal cancer surgery

  BMJ Open · 2025-01-01 · 3 citations

  articleOpen access

  OBJECTIVE: To develop and validate a risk prediction model related to inflammatory and nutritional indexes for postoperative pulmonary infection (POI) after radical colorectal cancer (CRC) surgery. DESIGN: Cross-sectional study. PARTICIPANTS: This study analysed 866 CRC patients after radical surgery at a tertiary hospital in China. METHODS: Univariable and multivariable logistic regression (LR) analyses were used to explore influence factors of POI. Predictive models were constructed using LR, random forest, support vector machine, K-nearest neighbours, naive Bayes and XGBoost. The LR model was used to generate a nomogram for POI prediction. The discrimination and calibration of the nomogram were assessed using receiver operating characteristic (ROC) curves and calibration curves. The contributions of inflammatory and nutritional indexes to the nomogram were evaluated through Net Reclassification Improvement and integrated discrimination improvement, while clinical practicability was assessed using decision curve analysis. MAIN OUTCOME MEASURES: POI during hospitalisation. RESULTS: Independent factors identified from multivariable LR for prediction POI included age, respiratory disease, Systemic Inflammation Response Index, albumin-to-globulin ratio, operative method and operative duration. The LR model demonstrated the best performance, with an area under the ROC curve of 0.773 (95% CI: 0.674 to 0.872). The nomogram has good differentiation ability, calibration and net benefit. Incorporating inflammatory and nutritional indexes into the nomogram enhanced predictive value compared with models excluding either factor. CONCLUSION: The nomogram related to inflammatory and nutritional indexes may represent a promising tool for predicting POI after radical surgery in CRC patients.

  PublisherOA PDFDOI

• Figure S1 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2025-04-03

  preprintOpen access

  <p>supplementary figure</p>

  PublisherDOI

• Figure S5 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2025-04-03

  preprintOpen access

  <p>Supplementary data</p>

  PublisherDOI

• Figure S4 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2025-04-03

  preprintOpen access

  <p>supplementary data</p>

  PublisherDOI

• IGFBP3–SphK1/S1P Signaling Axis Drives Enzalutamide Resistance in Advanced Prostate Cancer

  Molecular Cancer Therapeutics · 2025-12-04

  articleOpen access

  Enzalutamide resistance remains a significant challenge in the treatment of advanced prostate cancer. Identifying molecular drivers of enzalutamide resistance is crucial for developing effective therapeutic strategies. In this study, we identify insulin-like growth factor-binding protein 3 (IGFBP3) as a key driver of enzalutamide resistance in castration-resistant prostate cancer (CRPC). We demonstrate that IGFBP3 expression is significantly upregulated in enzalutamide-resistant C4-2B MDVR cells compared with parental C4-2B cells. This upregulation was consistently observed across multiple enzalutamide-resistant CRPC models, including LNCaP-derived 42D and 42F cells, as well as long-term enzalutamide-resistant cell lines derived from LNCaP, VCaP, LAPC-4, and CWR-R1 cells. Additionally, enzalutamide treatment directly induced IGFBP3 expression in sensitive cells. Elevated IGFBP3 expression was also observed in CRPC patient samples after enzalutamide treatment and was associated with higher Gleason scores and reduced disease-free survival. Mechanistically, IGFBP3 activates the sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway, which promotes cell survival and resistance to enzalutamide. IGFBP3 knockdown decreased SphK1 expression, reduced S1P secretion, and enhanced enzalutamide sensitivity, whereas IGFBP3 overexpression induced SphK1 expression and S1P production, conferring enzalutamide resistance. Inhibition of IGFBP3 via siRNA reduced cell viability, induced apoptosis, and resensitized resistant models to enzalutamide. Similarly, targeting SphK1 with the inhibitor SKI-II suppressed SphK1 activity, reduced S1P production, enhanced enzalutamide sensitivity, and significantly inhibited resistant tumor growth while enhancing enzalutamide sensitivity. Collectively, these findings highlight IGFBP3-mediated SphK1 signaling as a critical mediator of enzalutamide resistance and suggest that targeting the IGFBP3/SphK1/S1P axis represents a promising therapeutic strategy to overcome resistance in advanced prostate cancer.

  PublisherOA PDFDOI

• Figure S4 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2025-04-03

  preprintOpen access

  <p>supplementary data</p>

  PublisherDOI

• Correction: Novel inhibition of AKR1C3 and androgen receptor axis by PTUPB synergizes enzalutamide treatment in advanced prostate cancer

  Oncogene · 2025-04-10

  erratumOpen accessSenior author
  PublisherOA PDFDOI

• Figure S2 from PINK1-Mediated Mitochondrial Activity Confers Olaparib Resistance in Prostate Cancer Cells

  2025-04-03

  preprintOpen access

  <p>supplementary data</p>

  PublisherDOI

Recent grants

• Modulating HSP70/STUB1 machinery in therapy-resistant prostate cancer

  NIH · $1.8M · 2021–2026

• Dissecting the Role of Proteostasis in Anti-Androgen Resistant Prostate Cancer

  NIH · $1.8M · 2021–2026

Frequent coauthors

• Allen C. Gao

  VA Northern California Health Care System

  264 shared

• Christopher P. Evans

  UC Davis Comprehensive Cancer Center

  151 shared

• Wei Lou

  143 shared

• Joy C. Yang

  University of California, Davis

  116 shared

• Shu Ning

  91 shared

• Alan P. Lombard

  77 shared

• Nagalakshmi Nadiminty

  60 shared

• Pengfei Xu

  University of California, Davis

  60 shared

Education

• PhD, Oncology

  Sichuan University

  2012

• MD, Medicine

  Sichuan University

  2005

Awards & honors

• DoD PCRP Idea Development Award (2023)
• DoD PCRP Translational Scientific Award (2023)
• SBUR Young Investigator Award (2022)
• NCI Method to Extend Research in Time (MERIT)(R37) Award (20…
• NCI Paul Calabresi Clinical Oncology K12 Career Development…