To metabolomics and beyond: a technological portfolio to investigate cancer metabolism

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 22, 2023

Abstract Tumour cells have exquisite flexibility in reprogramming their metabolism order to support tumour initiation, progression, metastasis and resistance therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic redox status sustain increased energetic demand cells. Over last decades, cancer field has seen an explosion new biochemical technologies giving more tools than ever before navigate this complexity. Within cell or tissue, metabolites constitute direct signature molecular phenotype thus profiling concrete clinical applications oncology. Metabolomics fluxomics, are key technological approaches that mainly revolutionized enabling researchers both qualitative mechanistic model cancer. Furthermore, upgrade from bulk single-cell analysis provided unprecedented opportunity investigate biology at cellular resolution allowing depth quantitative complex heterogenous diseases. More recently, advent functional genomic screening allowed identification pathways, processes, biomarkers novel therapeutic targets concert with other allow patient stratification treatment regimens. This review is intended be guide for metabolism, highlighting current emerging technologies, emphasizing advantages, disadvantages potential leading development innovative anti-cancer

Язык: Английский

---

Role of p53 in breast cancer progression: An insight into p53 targeted therapy

Theranostics, Год журнала: 2023, Номер 13(4), С. 1421 - 1442

Опубликована: Янв. 1, 2023

The transcription factor p53 is an important regulator of a multitude cellular processes.In the presence genotoxic stress, activated to facilitate DNA repair, cell cycle arrest, and apoptosis.In breast cancer, tumor suppressive activities are frequently inactivated by either overexpression its negative MDM2, or mutation which present in 30-35% all cancer cases.Notably, frequency highly subtype dependent cancers, with majority hormone receptor-positive luminal subtypes retaining wild-type status while receptor-negative patients predominantly carry mutations gain-of-function oncogenic that contribute poorer prognosis.Thus, two-pronged strategy targeting mutant different can have clinical relevance.The development p53-based therapies has rapidly progressed recent years, include unique small molecule chemical inhibitors, stapled peptides, PROTACs, as well several genetic-based approaches using vectors engineered antibodies.In this review, we highlight therapeutic strategies pre-clinical overcome inactivation both p53-bearing tumors, discuss their efficacies limitations settings.

Язык: Английский

---

Therapeutics Targeting p53-MDM2 Interaction to Induce Cancer Cell Death

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 5005 - 5005

Опубликована: Апрель 30, 2022

Named as the guardian of genome, p53 is a tumor suppressor that regulates cell function, often through many different mechanisms such DNA repair, apoptosis, cycle arrest, senescence, metabolism, and autophagy. One genes activates MDM2, which forms negative feedback loop since MDM2 induces degradation p53. When activity inhibited, damaged cells do not undergo arrest or apoptosis. As 50% human cancers inactivate by mutation, current research focuses on reactivating developing drugs target p53-MDM2 interaction, includes binding phosphorylation The objective this article to provide short list description antagonists may be excellent candidates for inducing cancer death. Relevant articles were searched identified using online databases PubMed ScienceDirect. Increasing levels, targeting can help play its role induce Researchers have compounds act inhibitors, either directly modifying with phosphorylation. results associated demonstrate importance interactions inhibit growth, indicates use improve therapeutics.

Язык: Английский

---

The emerging role of ferroptosis in female reproductive disorders

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 166, С. 115415 - 115415

Опубликована: Сен. 4, 2023

Iron, as an essential trace element for the organism, is vital maintaining organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis a novel form of programmed cell death distinguished by overload lipid peroxidation, which unique from autophagy, apoptosis necrosis, more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis associated with development female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), cancer (OC), preeclampsia (PE) spontaneous abortion (SA). Pathways genes may participate in processes regulate granulosa proliferation secretion, oocyte development, reserve function, early embryonic placental oxidative stress. However, its exact mechanism has not been fully revealed. Therefore, our review systematically elaborates occurrence research progress FRDs, view to providing literature references clinical targeting -related pathways regulatory factors management FRDs.

Язык: Английский

---

The two sides of chromosomal instability: drivers and brakes in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 29, 2024

Abstract Chromosomal instability (CIN) is a hallmark of cancer and associated with tumor cell malignancy. CIN triggers chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes chromosomes. arises errors DNA replication segregation during division, formation abnormal and/or structure Errors result licensing as well stress, such double-strand breaks stalled forks; meanwhile, stem defects machinery, centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, defective sister chromatids cohesion. In cells, deleterious damage, proteotoxic metabolic alteration, cycle arrest, senescence. Paradoxically, despite these negative consequences, one hallmarks found over 90% solid tumors blood cancers. Furthermore, could endow enhanced adaptation capabilities due increased intratumor heterogeneity, thereby facilitating adaptive resistance therapies; however, excessive induce death, “just-right” model for tumors. Elucidating complex nature crucial understanding dynamics tumorigenesis developing effective anti-tumor treatments. This review provides an overview causes consequences CIN, paradox phenomenon that continues perplex researchers. Finally, this explores potential CIN-based therapy.

Язык: Английский

---

Molecular Mechanism of Natural Food Antioxidants to Regulate ROS in Treating Cancer: A Review

Antioxidants, Год журнала: 2024, Номер 13(2), С. 207 - 207

Опубликована: Фев. 6, 2024

Cancer is the second-highest mortality rate disease worldwide, and it has been estimated that cancer will increase by up to 20 million cases yearly 2030. There are various options of treatment for cancer, including surgery, radiotherapy, chemotherapy. All these have damaging adverse effects can reduce patient’s quality life. itself arises from a series mutations in normal cells generate ability divide uncontrollably. This cell mutation happen as result DNA damage induced high concentration ROS cells. High levels reactive oxygen species (ROS) cause oxidative stress, which initiate proliferation. On other hand, cytotoxic effect elevated be utilized anticancer therapy. Some bioactive compounds natural foods such fruit, vegetables, herbs, honey, many more identified promising source antioxidants prevent stress regulating level body. In this review, we highlighted discussed benefits antioxidant regulate through pathways.

Язык: Английский

---

Modified chitosan: Insight on biomedical and industrial applications

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 275, С. 133526 - 133526

Опубликована: Июль 2, 2024

Язык: Английский

---

Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 172, С. 116207 - 116207

Опубликована: Янв. 31, 2024

Lung cancer ranks among the most prevalent forms of and remains a significant factor in cancer-related mortality across world. It poses challenges to healthcare systems society as whole due its high incidence, rates, late-stage diagnosis. Resveratrol (RV), natural compound found various plants, has shown potential nanomedicine for lung treatment. RV varied effects on cells, including promoting apoptosis by increasing pro-apoptotic proteins (Bax Bak) decreasing anti-apoptotic (Bcl-2). also hinders cell proliferation influencing important signaling pathways (MAPK, mTOR, PI3K/Akt, Wnt/β-catenin) that govern progression. In addition, acts potent antioxidant, diminishing oxidative stress safeguarding cells against DNA damage. However, using alone treatment drawbacks, such low bioavailability, lack targeting ability, susceptibility degradation. contrast, nanoparticle-based delivery address these limitations hold promise improving outcomes cancer; nanoparticle formulations offer advantages improved drug delivery, increased stability, controlled release, targeted cells. This article will provide an overview cancer, explore therapeutic agent, discuss benefits highlight nanoparticles treatment, cancer. By optimizing clinical application, future studies aim enhance overall improve prognosis patients.

Язык: Английский

---

Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection

Antioxidants, Год журнала: 2024, Номер 13(5), С. 504 - 504

Опубликована: Апрель 23, 2024

Despite the significant progress in fields of biology, physiology, molecular medicine, and pharmacology; designation properties nitrogen monoxide regulation life-supporting functions organism; numerous works devoted to this molecule, there are still many open questions field. It is widely accepted that nitric oxide (•NO) a unique molecule that, despite its extremely simple structure, has wide range body, including cardiovascular system, central nervous system (CNS), reproduction, endocrine respiration, digestion, etc. Here, we systematize •NO, contributing conditions physiological norms, as well various pathological processes, mechanisms cytoprotection cytodestruction. Current experimental clinical studies contradictory describing role •NO pathogenesis diseases CNS. We describe cytoprotective action associated with expression antiapoptotic chaperone proteins mitochondrial function. The most prominent cytodestruction—the initiation nitrosative oxidative stresses, production reactive oxygen species, participation apoptosis mitosis. formation endothelial dysfunction also considered. Moreover, focus on ways pharmacological modulation nitroxidergic allow for decrease cytodestructive increase ones.

Язык: Английский

---

Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications

Cells, Год журнала: 2024, Номер 13(22), С. 1838 - 1838

Опубликована: Ноя. 6, 2024

Cell survival and death are intricately governed by apoptosis, a meticulously controlled programmed cell death. Apoptosis is vital in facilitating embryonic development maintaining tissue homeostasis immunological functioning. It complex interplay of intrinsic extrinsic signaling pathways that ultimately converges on executing the apoptotic program. The pathway initiated binding ligands such as TNF-α Fas to their respective receptors surface. In contrast, leads increased permeability outer mitochondrial membrane release apoptogenic factors like cytochrome c, which regulated Bcl-2 family proteins. Once activated, these lead cascade biochemical events, including caspase activation, DNA fragmentation, dismantling cellular components. Dysregulation apoptosis implicated various disorders, cancer, autoimmune diseases, neurodegenerative cardiovascular diseases. This article focuses elucidating molecular mechanisms underlying regulation, develop targeted therapeutic strategies. Modulating holds immense potential cancer treatment, where promoting malignant cells could tumor regression. demonstrates targeting providing options for treating neurological illnesses. safety effectiveness apoptosis-targeting drugs being assessed ongoing preclinical clinical trials (phase I-III), opening door more effective approaches better patient outcomes.

Язык: Английский

---