https://www.cancerbiologyresearch.com/

Cancer biology research, Rabat (2025)

15/10/2025

Harnessing Transposable Elements for Immunotherapy👇

✅1. From Discovery to Therapeutic Application
Transposable elements (TEs), long viewed as genomic "junk," are now emerging as powerful modulators of immune function. Basic research is uncovering how these mobile genetic elements can act as immune instructors, shaping responses in health and disease. This knowledge forms the foundation for their potential use in immunotherapy.

✅2. Insights from RNA-Seq and Gene Editing
Advanced RNA sequencing (RNA-seq), especially of intronic regions in immune cells under both normal and diseased states, is helping to map TE activity and understand their role in immune regulation. Once candidate TE insertion sites are identified, gene editing tools like CRISPR and base editors can validate their function—either activating, silencing, or modifying specific TEs to assess their immunological impact.

✅3. TEs as Disease Drivers and Therapeutic Targets
TEs may contribute to immune-related diseases such as autoimmunity or organ transplant rejection by acting as abnormal antigens. Validating this link is essential to designing therapies that can suppress or exploit these responses for therapeutic gain.

✅4. Precision Tools for TE Manipulation
To safely and effectively harness TEs, precise tools must be developed to modulate them in a tissue-, context-, and subfamily-specific manner. Emerging technologies, like the Mariner2_AG (MAG) transposon—a DNA TE outperforming traditional lentiviral vectors—are expanding our genetic engineering toolkit.

✅5. TE-Based Therapeutic Strategies
Manipulating TEs in key immune cells like hematopoietic stem cells (HSCs) or CAR-T cells may enhance their therapeutic functions, particularly in cancer. In diseases driven by abnormal TE activation, reverse transcriptase inhibitors or DNA methyltransferase (DNMT) agonists could restore balance. Conversely, drugs like DNMT or HDAC inhibitors can boost TE expression, generating tumor-specific neoantigens—offering a novel avenue for cancer immunotherapy.
💡 Schmidleithner, L., Stüve, P. & Feuerer, M. Transposable elements as instructors of the immune system. Nat Rev Immunol 25, 696–706 (2025)

15/10/2025

Layers of Transposable Element Influence on Cell Biology👇

✅1. Genomic Mobility and Gene Disruption
Transposable elements (TEs) can change their position within the genome, a process known as transposition. This movement can disrupt existing genes, interfere with regulatory sequences, or create new splice variants and genes. Such genomic rearrangements can contribute to genetic diversity, evolution, and in some cases, disease.

✅2. Transcriptional Activity and Functional RNA/Protein Products
TEs are not merely passive DNA elements—they can be transcribed into RNA or reverse-transcribed into cDNA. These RNA products, such as piwi-interacting RNAs (piRNAs), can bind to genomic regulatory elements and influence gene expression. Additionally, TE-derived RNAs can be sensed by innate immune receptors in the cytoplasm, triggering immune responses. Some TEs are even translated into proteins, which may be secreted, presented via MHC molecules, or act as transcriptional regulators. This diverse activity can impact cellular immunity and contribute to protein diversity through alternative exonization.

✅3. Cis-Regulatory Functions
Beyond transposition and transcription, TEs can act in cis to modulate gene expression. They can promote the formation of heterochromatin, a tightly packed form of DNA associated with gene silencing. By influencing the epigenetic landscape, TEs can shape transcriptional programs across the genome, affecting gene regulation in both development and disease.
💡 Schmidleithner, L., Stüve, P. & Feuerer, M. Transposable elements as instructors of the immune system. Nat Rev Immunol 25, 696–706 (2025).

14/10/2025

Protein Synthesis: From DNA to Functional Protein👇

✅Transcription:
In the nucleus, DNA is copied into RNA by RNA polymerase. The process includes initiation at the promoter, elongation of the RNA strand, and termination at specific signals. In eukaryotes, the pre-mRNA undergoes processing: 5′ capping, 3′ polyadenylation, and splicing to form mature mRNA.

✅Translation:
In the cytoplasm, ribosomes read the mRNA to assemble amino acids into a polypeptide chain. Translation starts at the AUG start codon, elongates by adding amino acids according to codons, and ends at a stop codon with release of the new protein.

✅Post-Translational Modifications (PTMs):
After translation, proteins may be modified to become functional. Common PTMs include phosphorylation, glycosylation, acetylation, proteolytic cleavage, ubiquitination, and lipidation. These modifications often occur in the endoplasmic reticulum and Golgi apparatus.
💡 images from Chemistry talk

14/10/2025

Genome-Wide Association Studies (GWAS)👇

✅Genome-wide association studies (GWAS) are research methods used to identify genetic variants associated with specific diseases or traits. They involve scanning the entire genome of many individuals to detect single-nucleotide polymorphisms (SNPs) that occur more frequently in people with a particular condition than in those without it.

✅By comparing genetic data across large populations, GWAS help pinpoint genomic regions linked to complex diseases such as cancer, diabetes, and heart disease. These studies provide valuable insights into disease mechanisms, potential biomarkers, and therapeutic targets. However, GWAS identify associations rather than causation, and follow-up functional studies are needed to confirm biological relevance.

13/10/2025

Allele Recombination👇

✅Recombination is the process by which alleles are rearranged into new combinations during meiosis, specifically through crossing over between homologous chromosomes.

✅As gametes form, segments of DNA can be exchanged between paired chromosomes. This reshuffling creates genetic diversity by producing new allele combinations not found in either parent.

✅Over two generations, recombination can result in:

🔴Parental (non-recombinant) combinations – when alleles are inherited in the same arrangement as the parent (lower left).

🔴Recombinant combinations – when crossing over leads to new arrangements of alleles (lower right).

🔴This process is crucial for genetic variation in populations and plays a key role in evolution and inheritance patterns.

13/10/2025

Genetic Linkage👇

✅Genetic linkage refers to the tendency of genes that are located close to each other on the same chromosome to be inherited together during meiosis. This occurs because such genes are less likely to be separated by recombination (crossing over) during the formation of gametes.

✅The closer two genes are on a chromosome, the stronger the linkage and the lower the chance of recombination between them. Genetic linkage was first observed by Thomas Hunt Morgan in fruit flies, leading to the development of genetic maps based on recombination frequencies.

✅Linkage analysis is widely used in genetics research and disease gene mapping, helping scientists identify regions of the genome associated with inherited traits or disorders.
Image from: BioNinja

13/10/2025

Targeting Energy Metabolism for Cardiovascular Disease Therapy👇

✅a. Enhancing Glycolysis
Various drugs can increase energy production in the heart by targeting the expression of glucose transport proteins and glycolytic enzymes. This metabolic shift helps support cardiac energy needs and reduces oxidative stress, improving overall heart function.

✅b. Inhibiting Fatty Acid Oxidation (FAO)
Medications that inhibit fatty acid oxidation, a highly oxygen-consuming process, can promote a shift toward glycolysis. This is particularly beneficial under hypoxic conditions, as glycolysis is more oxygen-efficient and helps maintain cardiac function when oxygen supply is limited.

✅c. Targeting Mitochondrial Function
Therapies that stabilize mitochondrial activity, particularly the TCA cycle and the electron transport chain, help reduce reactive oxygen species (ROS) production. This improves ATP generation and contributes to the maintenance of heart function and structural stability.

✅d. Supplementing with Alternative Energy Sources
Supplying external energy substrates, such as ketone bodies and branched-chain amino acids (BCAAs), can support cardiac metabolism. These substrates enhance energy synthesis and contribute to the functional stability of the heart, especially under stress or disease conditions.
💡 Liu, H., Wang, S., Wang, J. et al. Energy metabolism in health and diseases. Sig Transduct Target Ther 10, 69 (2025).

13/10/2025

Targeting Energy Metabolism for Cancer and Neurodegenerative Disease Therapy💡

✅Altered energy metabolism is a hallmark of both cancer and neurodegenerative diseases, but therapeutic strategies differ due to the distinct metabolic features of each condition.

🧬 Cancer: Targeting Glycolysis

Therapeutic Strategy: Inhibiting key glycolytic enzymes and transporters to disrupt cancer cell energy supply and biosynthesis.

Common Targets:

HK (Hexokinase): Inhibitors like 2-deoxyglucose (2-DG)

PFK (Phosphofructokinase) and PK (Pyruvate kinase): Glycolysis bottlenecks

LDH (Lactate dehydrogenase): Inhibitors reduce lactate production and tumor growth

GLUT (Glucose transporters): Block glucose uptake

These therapies aim to starve tumors, enhance sensitivity to chemo/radiotherapy, and reduce immune evasion by modifying the tumor microenvironment.

🧠 Neurodegenerative Diseases: Targeting Mitochondrial Metabolism

In neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and ALS, there is progressive mitochondrial dysfunction, leading to impaired oxidative phosphorylation (OXPHOS), increased ROS production, and neuronal energy failure.

Therapeutic Strategy: Support or restore mitochondrial function to preserve neuronal viability.

Common Approaches:

Mitochondrial antioxidants (e.g., MitoQ, CoQ10) to reduce oxidative stress

Enhancers of mitochondrial biogenesis, like PGC-1α activators

Complex I stimulators and ETC modulators to restore ATP production

NAD⁺ precursors (e.g., nicotinamide riboside) to support redox balance

These treatments focus on stabilizing mitochondrial function, reducing cell death, and slowing disease progression.

By targeting specific metabolic vulnerabilities—glycolysis in cancer and mitochondrial dysfunction in neurodegeneration—therapies can be tailored to the metabolic landscape of each disease.
💡Liu, H., Wang, S., Wang, J. et al. Energy metabolism in health and diseases. Sig Transduct Target Ther 10, 69 (2025).

13/10/2025

Methods for Detecting Energy Metabolism👇

Monitoring and analyzing energy metabolism is essential for understanding physiological and pathological processes, including cancer, heart disease, and autoimmune disorders. Several advanced techniques are used to assess metabolic activity, metabolite levels, and pathway alterations.

🔬 1. MRI (Magnetic Resonance Imaging)

Function: Provides non-invasive imaging of tissue structure and function.

Application: Magnetic resonance spectroscopy (MRS), a variant of MRI, can detect metabolic changes by measuring metabolites such as ATP, phosphocreatine, and lactate in tissues.

🧪 2. PET (Positron Emission Tomography)

Function: Visualizes and quantifies metabolic activity using radiolabeled tracers (e.g., ¹⁸F-FDG for glucose metabolism).

Application: Widely used to detect areas of high glycolysis in cancer, brain activity, or cardiac metabolism.

🧫 3. HPLC (High-Performance Liquid Chromatography)

Function: Separates and quantifies small molecules such as nucleotides, organic acids, and sugars.

Application: Used for profiling metabolites involved in glycolysis, TCA cycle, and nucleotide metabolism.

🌬️ 4. GC (Gas Chromatography)

Function: Separates volatile compounds for identification and quantification.

Application: Often used in combination with MS for analyzing fatty acids, amino acids, and organic acids in energy metabolism.

🧬 5. MS (Mass Spectrometry)

Function: Accurately measures the mass-to-charge ratio of metabolites.

Application: Allows for high-throughput, sensitive detection of a wide range of metabolic intermediates (e.g., ATP, acetyl-CoA, lactate).

⚗️ 6. CE-MS (Capillary Electrophoresis–Mass Spectrometry)

Function: Combines electrophoretic separation with mass analysis.

Application: Ideal for analyzing small, charged metabolites such as amino acids, TCA intermediates, and energy cofactors with high resolution.

These tools provide complementary insights into cellular and tissue-level metabolism, enabling researchers and clinicians to track metabolic shifts, diagnose disease, and monitor treatment response.
💡 Liu, H., Wang, S., Wang, J. et al. Energy metabolism in health and diseases. Sig Transduct Target Ther 10, 69 (2025).

12/10/2025

Energy Metabolism-Driven Alterations in the Tumor Microenvironment (TME)👇

✅Metabolic reprogramming in cancer cells profoundly reshapes the tumor microenvironment (TME), creating hostile conditions for immune cells while promoting tumor growth and immune evasion.

✅a. Warburg Effect and Glucose Competition

🔴Cancer cells preferentially undergo aerobic glycolysis (Warburg effect), consuming large amounts of glucose and depleting it from the surrounding microenvironment. This causes metabolic competition between cancer cells and immune cells like activated T cells, NK cells, and M1 macrophages, impairing their energy production and immune functions.

🔴Excess glycolysis leads to lactate accumulation and a decrease in extracellular pH. The resulting acidic environment suppresses the cytotoxic activity of immune cells by reducing secretion of inflammatory cytokines, perforin, and granzymes. In contrast, lactate supports the survival and function of immunosuppressive cells such as M2 macrophages, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and cancer-associated fibroblasts (CAFs)—partly through increased expression of glucose transporters and MCT-1, facilitating lactate uptake and metabolic adaptation.

✅b. Mitochondrial OXPHOS and Metabolic Intermediates

🔴Alterations in mitochondrial oxidative phosphorylation (OXPHOS) lead to the accumulation of metabolites like acetyl-CoA, succinate, and fumarate. These intermediates act as signaling molecules that promote epithelial-mesenchymal transition (EMT), enhancing the invasive potential of cancer cells.

🔴Furthermore, these metabolites stimulate the secretion of TGF-β and IL-8, which recruit immunosuppressive cells such as Tregs and MDSCs, contributing to immune suppression and tumor progression.

✅c. Fatty Acid Oxidation (FAO) and CD36 Expression

🔴Enhanced fatty acid oxidation (FAO) in the TME supports the metabolic needs of Tregs, M2 macrophages, and cancer cells. This is associated with increased expression of CD36, a fatty acid transporter.

🔴While FAO supports energy production in immunosuppressive cells, it exerts an inhibitory effect on the metabolism and function of activated T cells and dendritic cells (DCs), further tipping the balance in favor of immune evasion.

✅d. Glutaminolysis and Immune Suppression

🔴Cancer cells increase glutaminolysis, rapidly consuming glutamine in the TME. This leads to glutamine depletion, impairing the function of activated T cells and NK cells by reducing the production of pro-inflammatory cytokines such as TNF-α and IFN-γ.

🔴As a result, immune surveillance weakens, and immune escape mechanisms are reinforced, enabling tumor progression.

✅Overall, metabolic remodeling in the TME not only fuels tumor cell survival and metastasis but also creates a suppressive metabolic environment that hampers anti-tumor immunity.
💡 Liu, H., Wang, S., Wang, J. et al. Energy metabolism in health and diseases. Sig Transduct Target Ther 10, 69 (2025).

12/10/2025

Energy Metabolism in Cancer👇

✅Cancer cells undergo profound metabolic reprogramming to support rapid growth and survival under stress. This reprogramming involves a shift in energy production pathways and is tightly regulated by oncogenic and tumor-suppressive signaling networks.

✅One hallmark of cancer metabolism is enhanced glycolysis—even in the presence of oxygen—known as the Warburg effect. Key glycolytic transporters and enzymes such as GLUT, hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) are upregulated, increasing glucose uptake and lactate production.

✅Glutamine metabolism is also elevated. Glutamine transporters and glutaminase (GLS) are upregulated, catalyzing glutamine’s conversion to glutamate, which is further used for biosynthesis or ATP generation via alternative pathways.

✅Fatty acid metabolism is reprogrammed as well. The expression of fatty acid transport proteins (e.g., CD36) and enzymes involved in fatty acid synthesis such as ACLY, ACC, FASN, and ACS is increased, supporting membrane formation and signaling.

✅In contrast, TCA cycle and oxidative phosphorylation (OXPHOS) are often suppressed in cancer cells. The activity of mitochondrial enzymes including isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), fumarate hydratase (FH), and malate dehydrogenase (MDH) is downregulated or inhibited.

✅This altered metabolism is orchestrated by various signaling molecules:

🔴Oncogenes and pro-oncogenic pathways (red box):

HIF1-α, KRAS, SALL4, c-MYC, PI3K/AKT, and mTOR promote glycolysis, glutaminolysis, and fatty acid synthesis, while inhibiting the TCA cycle and OXPHOS.

🔴Tumor suppressors (blue box):

P53, PTEN, AMPK, NRF2, and PGC1α counteract this by inhibiting glycolysis and lipid synthesis and enhancing mitochondrial respiration and oxidative metabolism.

✅Together, these metabolic adaptations provide cancer cells with the necessary energy and building blocks for uncontrolled growth, resistance to cell death, and adaptation to nutrient-deprived environments.
Liu, H., Wang, S., Wang, J. et al. Energy metabolism in health and diseases. Sig Transduct Target Ther 10, 69 (2025).

12/10/2025

Energy Metabolism in Autoimmune Diseases👇

✅In autoimmune diseases, dysregulated energy metabolism in immune cells plays a central role in driving chronic inflammation and tissue damage.

✅CD4⁺ T cells may enhance both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) under certain pathological conditions. However, in rheumatoid arthritis (RA), these T cells exhibit impaired mitochondrial OXPHOS and shift toward the pentose phosphate pathway (PPP) to meet biosynthetic and redox needs.

✅Naive Th cells and B cells typically rely on aerobic oxidation, whereas activated Th and B cells favor glycolysis to support rapid proliferation and effector function.

✅Regulatory T cells (Tregs) can utilize both glycolysis and lactate within the tumor microenvironment (TME) to sustain their immunosuppressive activity.

✅Macrophage metabolism is also polarized: M1 macrophages depend on aerobic glycolysis, supporting pro-inflammatory responses, while M2 macrophages utilize OXPHOS, aiding in tissue repair and anti-inflammatory functions.

✅Fibroblast-like synoviocytes (FLSs) undergo metabolic reprogramming in autoimmune settings, particularly in RA, shifting toward increased glycolysis, contributing to synovial hyperplasia and joint destruction.

✅Dendritic cells (DCs), as antigen-presenting cells, also alter their metabolic programs—adjusting OXPHOS and glycolysis pathways—upon activation, influencing their capacity to stimulate immune responses.

✅These metabolic changes in immune and stromal cells promote fibrosis, angiogenesis, and sustain chronic inflammation, ultimately exacerbating autoimmune pathology.
💡 Liu, H., Wang, S., Wang, J. et al. Energy metabolism in health and diseases. Sig Transduct Target Ther 10, 69 (2025).

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