Metabolic interrogation as a tool to optimize chemotherapeutic regimens
Vlad C Sandulache1,2, Yunyun Chen1, Lei Feng3
1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncotarget
|February 11, 2017
Summary
Measuring lactate levels can predict how well platinum-based chemotherapy works. This metabolic biomarker helps personalize cancer treatment by tracking real-time effects on tumor growth and cell death.
Area of Science:
- Biochemistry
- Oncology
- Metabolomics
Background:
- Platinum-based chemotherapy is a cornerstone in cancer treatment.
- Identifying biomarkers for treatment response is crucial for personalized medicine.
- Cellular metabolism influences platinum compound efficacy.
Purpose of the Study:
- To investigate if metabolic interrogation, specifically lactate production, can predict platinum-based chemotherapy effectiveness.
- To explore lactate levels as a real-time biomarker for treatment response in head and neck squamous cell carcinoma (HNSCC).
Main Methods:
- Assessed effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, cell death, and lactate production in vitro.
- Utilized dual flank xenograft tumor models to correlate lactate levels with tumor growth delay.
- Tested lactate interrogation for predicting doxorubicin effects in HNSCC and acute myelogenous leukemia (AML) cell lines.
Main Results:
- Platinum compounds induced a transient, dose-dependent drop in lactate production, correlating with DNA damage and cell death.
- Lactate production changes predicted differential sensitivity to CDDP vs. CBP and p53-mediated resistance.
- In vivo, platinum-induced lactate level changes correlated with tumor growth delay, defining metabolic stress profiles.
- Lactate interrogation predicted doxorubicin efficacy in both solid tumors and leukemia.
Conclusions:
- Real-time monitoring of lactate levels reflects chemotherapy's impact on DNA damage, cell death, and tumor growth.
- Lactate levels serve as a novel, real-time biomarker for chemotherapy effectiveness.
- This biomarker facilitates the development of adaptive, personalized treatment regimens for various malignancies.
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