Related Experiment Video
Updated: Jan 6, 2026
07:08
Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets
Published on: February 2, 2024
1.3K
Prognostic Impact of DPP4 Inhibitors on Systemic Drug Therapy for Advanced Kidney Cancer Patients
Shuhei Kamada1,2,3, Sachi Kitayama1,3, Ryosuke Yamase1,2
1Division of Systems Medicine and Gene Therapy, Saitama Medical University, Saitama, Japan.
Cancer Science
|November 19, 2025
Summary
Dipeptidyl peptidase 4 inhibitors (DPP4i) may improve systemic therapy outcomes for advanced renal cell carcinoma (RCC). DPP4i treatment was associated with longer survival and greater tumor shrinkage in RCC patients receiving TKIs or ICIs.
Area of Science:
- Oncology
- Pharmacology
- Immunotherapy
Background:
- Advanced renal cell carcinoma (RCC) treatment faces challenges despite tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).
- Previous research indicated dipeptidyl peptidase 4 inhibitors (DPP4i) enhance TKI sensitivity in RCC models.
Purpose of the Study:
- To evaluate the clinical utility of DPP4i in enhancing systemic therapy for advanced RCC, including ICIs.
- To identify prognostic factors associated with DPP4i use in RCC patients.
Main Methods:
- Retrospective analysis of 320 RCC patients undergoing systemic therapy.
- Cox proportional hazards model to assess prognostic factors.
- RNA sequencing analysis of RCC tumors from clinical trials (CheckMate-009, 010, 025).
Main Results:
- DPP4i treatment correlated with significantly longer overall survival (HR: 0.50, p=0.0060).
- Favorable prognostic factors included DPP4i use, BMI ≥25, no metastasis, low LDH, and low CRP.
- Patients receiving DPP4i showed more pronounced tumor shrinkage with first-line TKI or ICI therapy.
- DPP4-high RCC tumors displayed reduced immune infiltration and lower effector T cell signatures.
Conclusions:
- DPP4i may be a beneficial adjunct to systemic therapies like TKIs and ICIs in advanced RCC.
- Findings suggest a re-evaluation of type 2 diabetes mellitus's prognostic impact on RCC.
- Supports initiating clinical trials for concurrent DPP4i and RCC treatment strategies.
Related Concept Videos
01:23Dipeptidyl Peptidase 4 Inhibitors
540
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
540
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
238
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
238
01:28Chronic Kidney Disease III: Interprofessional Care
316
Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
316
01:24Glucagon-like Receptor Agonists
809
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
809
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
181
In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
181
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
554
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
554