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SDIRSACR Oncology Insights

L29

Tumor metabolism in the picture: Tracing and visualizing the metabolic alterations in cancer

Büşra KÖSE DEMİRTAŞ 1

1 Istinye University, Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Turkiye

Keywords: cancer, metabolism, mass spectrometry imaging, spatial metabolomics, metabolic flux

Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the demands of rapid proliferation,
survival in hostile microenvironments, and therapeutic resistance. This lecture will explore how advanced metabolomics
approaches are employed to dissect these metabolic alterations in cancer. Steady-state metabolomics allows for the
quantitative profiling of a snapshot of intracellular metabolites, revealing pathway enrichment and dysregulations.
Stable-isotope tracing provides dynamic insights into carbon and nitrogen fluxes through metabolic networks,
identifying nutrient preferences and pathway plasticity in cancer cells. Meanwhile, spatial metabolomics, by mass
spectrometry imaging (MSI), offers a visualization of the metabolic heterogeneity spatially resolved within tumors
and the tumor microenvironment. By integrating these methodologies, researchers can not only quantify metabolic
fluxes and pathway dependencies but also visualize spatial metabolic heterogeneity within tumors and systematically
characterize the metabolic dependencies of cancer cells to uncover context-specific vulnerabilities. In this session,
selected research studies will be discussed to illustrate how these tools are used in experimental designs to study
tumor progression, therapeutic responses and metabolic adaptation, providing a functional framework for targeting
cancer metabolism.

L30
Changes in tumor metabolism, consequences, and therapeutic opportunities

Alexey Bogdanov1

1 N.P. Napalkov Saint Petersburg Clinical Research and Practical Center of Specialized Types of Medical Care (Oncological), Saint
Petersburg, Russia

Keywords: acidosis, alkalization treatment, cancer metabolism, sodium bicarbonate, tumor microenvironment

Cancer cells undergo profound metabolic reprogramming to sustain their rapid proliferation and adapt to stressful
microenvironmental conditions. In addition to the well-known Warburg effect—where tumor cells preferentially
utilize aerobic glycolysis over oxidative phosphorylation—even more metabolic alterations occur, such as enhanced
glutaminolysis, dysregulated lipid metabolism, altered one-carbon metabolism, and modified mitochondrial function.
A major consequence of this metabolic shift is the acidification of the tumor microenvironment. High rates of glycolysis
lead to excessive lactate production and proton accumulation, resulting in an extracellular pH typically ranging from
6.5 to 6.9—considerably lower than the neutral pH (~7.4) of normal tissues. This acidic environment fosters tumor
progression by enhancing invasion and metastasis through the activation of matrix metalloproteinases, which degrade
the extracellular matrix. Moreover, acidosis impairs immune surveillance by suppressing the function of cytotoxic T
cells and natural killer cells, allowing cancer cells to evade immune detection and destruction. Tumor acidity also
contributes significantly to therapeutic resistance. Acidic conditions reduce the efficacy of chemotherapy and radiation
therapy, partly by activating survival pathways such as HIF-1α, NF-κB, and autophagy.
Given these challenges, targeting tumor acidity has emerged as a promising therapeutic strategy. One approach
involves using sodium bicarbonate (NaHCO₃), a simple alkalizing agent capable of selectively neutralizing extracellular
acid without altering systemic pH. Preclinical studies have shown that oral NaHCO₃ can raise tumor extracellular pH,
inhibit metastasis, and enhance the effectiveness of chemotherapy. In addition, localized delivery methods such as
intraperitoneal perfusion of NaHCO₃ have been explored, particularly in preclinical models of peritoneal carcinomatosis.
This approach improves drug penetration into tumor nodules, and enhances chemotherapeutic efficacy, with minimal
risk of systemic alkalosis.
Clinical evidence remains limited but encouraging. Pilot trials suggest that bicarbonate supplementation is safe and
may delay disease progression or stabilize advanced cancers when used as an adjuvant. Although larger clinical trials

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