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Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

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… Abbreviations: AC, adenylyl cyclase; ACBP, acyl‐CoA‐binding protein; APO‐A5, apolipoprotein A5; cAMP, cyclic adenosine monophosphate; CPT‐2, carnitine palmitoyltransferase 2; GPCR, G protein‐coupled receptor; MMP1, matrix metalloproteinase 1; PGAR, PPAR gamma angiopoietin‐related gene; PKA protein kinase …

Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy.

The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogram

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… An important role of FAO key enzyme, carnitine palmitoyl transferase 1a (CPT-1a) has been demonstrated in cancer cell survival in conditions of energy stress as it rewires the cancer cell metabolism ( 315 , 316 ). …

Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance.

Cancer remains a leading cause of mortality worldwide, with rising incidence and death rates continuing to rise. While conventional treatments such as surgery, radiotherapy, and chemotherapy form the backbone of cancer care, they are often limited by adverse effects, recurrence risk, and incomplete tumor eradication. Tumor immunotherapy-particularly immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapy-has emerged as a transformative approach by activating and reprogramming anti-tumor immune responses. Despite these advances, significant challenges persist, including

Radiation-Induced Oral Mucositis.

Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with

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… Vitamin E and l-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression: a controlled study in a rat model. J Radiat Res (2006) 47(1):91–102. 10.1269/jrr.47.91 32. Schmidt W, Rainville LC, McEneff G, Sheehan D, Quinn B. …

Role of mitochondria in physiological activities, diseases, and therapy.

Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of

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… Research has demonstrated that decanoylcarnitine can enhance mitochondrial energy supply and promote mitochondrial homeostasis by activating the PPARα-carnitine palmitoyltransferase 1 A (CPT1A) signaling pathway. …

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving

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… Key enzymes in fatty acid metabolism, such as ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), carnitine palmitoyltransferase (CPT), and different chain-length acyl-CoA dehydrogenases (ACADS, ACADM, ACADL, ACADVL), desaturases (SCD, FADS1, FADS2), and elongase play … Carnitine palmitoyltransferase 1B (CPT1B) is a key enzyme encoding FAO. The JAK/STAT3 signaling pathway regulates lipid metabolism, with the STAT3-CPT1B-FAO pathway promoting cancer cell stemness and chemotherapy resistance. …

Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.

Ammonium metabolism represents a critically understudied yet pivotal driver of prostate tumorigenesis and tumor microenvironment (TME) remodeling. The interplay between tumor metabolic reprogramming and the tumor microenvironment has emerged as a critical frontier in oncology research. While previous studies on prostate cancer metabolism have predominantly focused on lipid metabolism and the Warburg effect, the role of ammonium metabolism, particularly the urea cycle in tumor immune regulation remains insufficiently explored. This metabolic reprogramming constitutes a central node connecting c

Influence of the Mediterranean Diet on Healthy Aging.

The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologi

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… Compared to the Western diet, the MedDiet has significantly lower contents of choline and L-carnitine (present in egg, cheese, and red meat), and the production of TMAO by the microbiota has been shown to be lower [ 350 ]. …

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

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… It lowered pro-inflammatory cytokine levels of IL-1β and TNF-α and enhanced carnitine palmitoyl transferase 1A (CPT1A) and lysophosphatidylcholine acyltransferase 3 (LPCAT3), thereby attenuating the anti-proliferative effect of SIN (2.5 mM) on human colon cancer cells (HT-29, HCT-116, and SW-480) [ 41 …

The IL-17 family in diseases: from bench to bedside.

The interleukin-17 (IL-17) family comprises six members (IL-17A-17F), and recently, all of its related receptors have been discovered. IL-17 was first discovered approximately 30 years ago. Members of this family have various biological functions, including driving an inflammatory cascade during infections and autoimmune diseases, as well as boosting protective immunity against various pathogens. IL-17 is a highly versatile proinflammatory cytokine necessary for vital processes including host immune defenses, tissue repair, inflammatory disease pathogenesis, and cancer progression. However, ho

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… Thus, the absence of either TRAF3 or TRAF4 increases the expression of IL-17-dependent target genes, resulting in an enhanced IL-17-mediated inflammatory response. 46 , 62 Induction of IκBζ by IL-17 in fibroblastic reticular cells induces the production of carnitine palmitoyltransferase 1A (CPT1A), …

The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.

In order to effectively manage and cure cancer we should move beyond the general view of cancer as a random process of genetic alterations leading to uncontrolled cell proliferation or simply a predictable evolutionary process involving selection for traits that increase cell fitness. In our view, cancer is a systemic disease that involves multiple interactions not only among cells within tumors or between tumors and surrounding tissues but also with the entire organism and its internal "milieu". We define the internal body climate as an emergent property resulting from spatial and temporal in

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… More recently, variations in levels of glycine, serine, sphyngomyelin and free carnitine were linked to endometrial cancer development ( 75 ). …

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

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… Using nanoflow ultraperformance LC coupled to high-resolution orbitrap MS, carnitine and acetylcarnitine were identified as potential biomarkers for NDMM and relapsed MM [ 318 ]. …

Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.

Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectivene

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… synthetase; ASS1, argininosuccinate synthetase 1; ATP, adenosine triphosphate; CAIX, carbonic anhydrase IX; CA XII, carbonic anhydrase XII; CB-839, telaglenastat; CD36, cluster of differentiation 36; CD38, cluster of differentiation 38; CD39/CD73, ectonucleotidases; COX-2, cyclooxygenase-2; CPT1A, carnitine … synthetase; ASS1, argininosuccinate synthetase 1; ATP, adenosine triphosphate; CAIX, carbonic anhydrase IX; CA XII, carbonic anhydrase XII; CB-839, telaglenastat; CD36, cluster of differentiation 36; CD38, cluster of differentiation 38; CD39/CD73, ectonucleotidases; COX-2, cyclooxygenase-2; CPT1A, carnitine …

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer.

Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhan

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… Rb: Retinoblastoma protein; Bcl-xL: B-cell lymphoma extra large; Bax: Bcl-2-associated X protein; ALT: Alanine aminotransferase; MDA: Malondialdehyde; IL-1β: Interleukin 1 beta; HIF-α: Hypoxia-inducible factor 1-alpha; LDH: Lactate dehydrogenase; TG: Triglyceride; FASN: Fatty acid synthase; CPT1A: Carnitine …

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil

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… Inhibitors of lipid metabolism, such as the fatty acid synthase inhibitor C75 or the carnitine palmitoyltransferase I inhibitor etomoxir, can impair lipid biosynthesis and mitochondrial function, leading to increased DNA damage and enhanced PARPi sensitivity ( Figure 4 ) [ 206 , 207 ]. …

Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.

The dynamic changes in chromatin conformation alter the organization and structure of the genome and further regulate gene transcription. Basically, the chromatin structure is controlled by reversible, enzyme-catalyzed covalent modifications to chromatin components and by noncovalent ATP-dependent modifications via chromatin remodeling complexes, including switch/sucrose nonfermentable (SWI/SNF), inositol-requiring 80 (INO80), imitation switch (ISWI) and chromodomain-helicase DNA-binding protein (CHD) complexes. Recent studies have shown that chromatin remodeling is essential in different stag

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… A recent phase II trial with a combination of N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine recruits patients to study metabolic improvements in AD and PD subjects ( NCT04044131 ), and another phase II trial using NAM for AD treatment is also ongoing ( NCT03061474 ). …

Systematic review of the tools and outcomes for the assessment of acute radiation dermatitis severity.

Acute radiation dermatitis (ARD) is a common adverse effect experienced by patients undergoing radiation therapy. Effective assessment tools to accurately measure and manage ARD's impact on patients' quality of life and treatment outcomes is needed. The aim of this study was to evaluate the diverse tools and outcome measures used in the assessment of ARD. A systematic review of MEDLINE®, Embase, and Cochrane was conducted for records 1946-March 2024. A total of 423 studies, including 227 randomized controlled trials (RCTs), were included in the analysis. The review identified 58 distinct tools

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

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… For instance, depletion of carnitine acetyltransferase (CRAT) in cardiomyocytes enhances cholesterol catabolism, inducing mtDNA stress and triggering a cGAS-STING-driven IFN-I response. …

Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children. Despite this, very little improvement in survival rates has been achieved over the past few decades. This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years. In the past 20 years, research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell prolife