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Oxidative Stress Linking Obesity and Cancer: Is Obesity a 'Radical Trigger' to Cancer?

Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer

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… Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N. Engl. J. Med. 2005 352 987 996 10.1056/NEJMoa043330 15758009 147. Poon M.T.C. Sudlow C.L.M. Figueroa J.D. Brennan P.M. …

Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.

Cancer manifestation is a multistep process involving accumulation of various genetic and epigenetic changes that results in oncogenic "hallmarks of cancer" processes including genomic instability. Exploitation of aberrant DNA-damage response (DDR) mechanisms in cancer is in part a goal of many therapeutic strategies, and recent evidence supports the role of targeting DDR in modulating the tumor immune microenvironment to enhance immunotherapeutic response. Improved cancer profiling, including next-generation and whole-genome mutational sequencing of tumor tissue, as well as circulating nuclei

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… with RS or HRD | LY2606368 (prexasertib) | ORR, OS | 2 NCT04023669 | Medulloblastoma | Prexasertib | Safety and tolerability, ORR, DOR, PFS | 1 NCT05275426 | Ewing sarcoma | LY2880070 | ORR | 2 DNA-PK inhibitors NCT04555577 | MGMT unmethylated glioblastoma or gliosarcoma | Nedisertib + RT + surgery + temozolomide …

T-Regulatory Cells In Tumor Progression And Therapy.

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic ef

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… of tumor volume in murine cancer models. 62 , 63 A phase-I/II study with daclizumab (that blocks CD25) in combination with the DC vaccine has shown a transient but complete depletion of CD25 high cells in melanoma patients. 64 Similarly, in metastatic melanoma patients (with lymphopenia induced via temozolomide …

Current Status of Gene Engineering Cell Therapeutics.

Ex vivo manipulations of autologous patient's cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to in

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… Finally, a recent phase III trial has evaluated CIK immunotherapy with radiotherapy-temozolomide (TMZ) versus TMZ alone for the treatment of newly diagnosed glioblastomas ( 90 ). A total of 180 patients were randomly assigned to the CIK immunotherapy ( n = 91) or control group ( n = 89). …

Skeletal metastasis: treatments, mouse models, and the Wnt signaling.

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process o

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… screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer J Urol 2012 188 103 109 22583636 10.1016/j.juro.2012.03.008 PMC3473078 196 Palma JP Wang YC Rodriguez LE ABT-888 confers broad in vivo activity in combination with temozolomide …

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

Emerging and underexplored ginsenosides in cancer therapy (2020-2025): Beyond cytotoxic mechanisms.

Ginsenosides from Panax plants have long been studied as potential anticancer agents. In earlier years, most research focused on a few well-known ginsenosides that showed strong direct cytotoxicity, such as Rg3 and Rh2. As a result, many other ginsenosides were considered less active and received limited attention. However, studies published between 2020 and 2025 indicate that several previously underexplored ginsenosides also exhibit meaningful anticancer activity. These compounds often do not function as strongly cytotoxic agents. Instead, they act through broader and more indirect mechanism

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… Hypoxia-inducible factor-1 alpha MDSC | Myeloid-derived suppressor cell PARP | Poly(ADP-ribose) polymerase EGFR | Epidermal growth factor receptor TKIs | Tyrosine kinase inhibitors DOX | Doxorubicin PTX | Paclitaxel GEM | Gemcitabine DDP | Cisplatin (cis-diamminedichloroplatinum II) 5-FU | 5-Fluorouracil TMZ | Temozolomide …

Histone deacetylase 6: A new player in oxidative stress‑associated disorders and cancers (Review).

Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a crucial role in regulating the cellular response to oxidative stress. Unlike other HDACs, HDAC6 primarily deacetylates non‑histone proteins, influencing various cellular functions critical to the pathogenesis of numerous oxidative stress‑related diseases. This review summarizes the latest research on how HDAC6 affects oxidative stress pathways and its impact on diseases such as neurodegeneration, cancer and cardiovascular disorders. Additionally, the therapeutic potential of targeting HDAC6, as evide

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… Dual inhibition of CYP17A1 and HDAC6 by abiraterone-installed hydroxamic acid overcomes temozolomide resistance in glioblastoma through inducing DNA damage and oxidative stress. Cancer Lett. 2024;586:216666. doi: 10.1016/j.canlet.2024.216666. 111. …

Exploration of Site-Specific Drug Targeting-A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment.

Cancer has been one of the most dominant causes of mortality globally over the last few decades. In cancer treatment, the selective targeting of tumor cells is indispensable, making it a better replacement for conventional chemotherapies by diminishing their adverse side effects. While designing a drug to be delivered selectively in the target organ, the drug development scientists should focus on various factors such as the type of cancer they are dealing with according to which drug, targeting moieties, and pharmaceutical carriers should be targeted. All published articles have been collecte

Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside.

Cancer is a multifaceted global health issue and one of the leading causes of death worldwide. In recent years, medical science has achieved great advances in the diagnosis and treatment of cancer. Despite the numerous advantages of conventional cancer therapies, there are major drawbacks including severe side effects, toxicities, and drug resistance. Therefore, the urgency of developing new drugs with low cytotoxicity and treatment resistance is increasing. Antimicrobial peptides (AMPs) have attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tu

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… Despite standard treatments for newly diagnosed patients with GBM, such as total surgical resection, radiotherapy, and temozolomide (TMZ), it has faced the highest mortality rate with a postdiagnostic median survival of 12 to 15 months ( 128 , 129 ). …

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

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… Impact of Angiogenesis Inhibition by Sunitinib on Tumor Distribution of Temozolomide. Clin. Cancer Res. 2008;14:1540–1549. doi: 10.1158/1078-0432.CCR-07-4544. 208. Wildiers H., Guetens G., De Boeck G., Verbeken E.K., Landuyt B., Landuyt W., De Bruijn E.A., Van Oosterom A.T. …

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

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… DNA Repair in Personalized Brain Cancer Therapy with Temozolomide and Nitrosoureas. DNA Repair 78, 128–141. 10.1016/j.dnarep.2019.04.007 Kantarjlan H., Issa J. P., Rosenfeld Craig. S., Bennett J. M., Maher A., DiPersio J., et al. (2006). …

Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications.

Iron and ascorbic acid (vitamin C) are essential nutrients for the normal growth and development of humans, and their deficiency can result in serious diseases. Their interaction is of nutritional, physiological, pharmacological and toxicological interest, with major implications in health and disease. Millions of people are using pharmaceutical and nutraceutical preparations of these two nutrients, including ferrous ascorbate for the treatment of iron deficiency anaemia and ascorbate combination with deferoxamine for increasing iron excretion in iron overload. The main function and use of vit

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… Phase II Trial of Arsenic Trioxide and Ascorbic Acid with Temozolomide in Patients with Metastatic Melanoma with or Without Central Nervous System Metastases. Melanoma Res. 2008;18:147–151. doi: 10.1097/CMR.0b013e3282f2a7ae. 27. …

BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.

The BCL-2 family of proteins plays a central role in the regulation of apoptosis, with BCL-2 and BCL-xL representing two of its most prominent antiapoptotic members. This review explores the molecular regulation of BCL-2 and BCL-xL genes, emphasizing the structural domains that define the functions of the broader BCL-2 family. Beyond their canonical roles in preventing mitochondrial outer membrane permeabilization, both proteins contribute significantly to cancer development. Their overexpression enhances invasiveness and tumor progression, supports angiogenesis, and critically modulates cellu

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… Additionally, studies testing AT-101 with Temozolomide with or without radiotherapy ( NCT00390403 ), Erlotinib ( NCT00934076 ), Lenalidomide ( NCT01003769 [ 296 ]), and Rituximab ( NCT00286780 , NCT00440388 ) were withdrawn or terminated with no published results. …

Epigenetics-targeted drugs: current paradigms and future challenges.

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifyin

From Pioneering Discoveries to Innovative Therapies: A Journey Through the History and Advancements of Nanoparticles in Breast Cancer Treatment.

Nanoparticle technology has revolutionized breast cancer treatment by offering innovative solutions addressing the gaps in traditional treatment methods. This paper aimed to comprehensively explore the historical journey and advancements of nanoparticles in breast cancer treatment, highlighting their transformative impact on modern medicine. The discussion traces the evolution of nanoparticle-based therapies from their early conceptualization to their current applications and future potential. We initially explored the historical context of breast cancer treatment, highlighting the limitations

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… For example, vincristine-loaded solid lipid NPs (VCR-SLNs) efficiently deliver vincristine and temozolomide into U87MG glioblastoma cells, exhibiting higher cytotoxicity than single-drug SLNs. 143 The co-encapsulation of multiple chemotherapeutics within a single NP helps circumvent resistance pathways …

Current and Emerging Therapies for Targeting the ERK1/2 & PI3K Pathways in Cancer.

The ERK1/2 and PI3K signaling pathways play important roles in cellular proliferation, survival, differentiation, and metabolism. In cancer, these pathways are frequently dysregulated and overactivated, resulting in poor patient prognosis and resistance to treatment. These pathways are activated by receptor tyrosine kinases and send downstream signals to effectors such as RAS, RAF, MEK, AKT, and mTOR. In this review, we highlight the key components of the ERK1/2 and PI3K pathways, the roles they play in tumor progression, and the development of inhibitors and combination therapies designed to

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… Temozolomide, which is used along with radiotherapy, has been shown to be less effective in patients who lose PTEN function. This represents a major challenge in treatment as 40% of patients lose PTEN function [ 129 ]. …

Ferroptosis: Frenemy of Radiotherapy.

Recently, it was established that ferroptosis, a type of iron-dependent regulated cell death, plays a prominent role in radiotherapy-triggered cell death. Accordingly, ferroptosis inducers attracted a lot of interest as potential radio-synergizing drugs, ultimately enhancing radioresponses and patient outcomes. Nevertheless, the tumor microenvironment seems to have a major impact on ferroptosis induction. The influence of hypoxic conditions is an area of interest, as it remains the principal hurdle in the field of radiotherapy. In this review, we focus on the implications of hypoxic conditions

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… Sulfasalazine and Temozolomide with Radiation Therapy for Newly Diagnosed Glioblastoma. Neurol. India. 2014;62:42. doi: 10.4103/0028-3886.128280. 84. Nie D., Chen C., Li Y., Zeng C. …

Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.

Prostate cancer (PC) is the second most common cancer in men worldwide. More than 65% of men diagnosed with PC are above 65. Patients with localized PC show high long-term survival, however with the disease progression into a metastatic form, it becomes incurable, even after strong radio- and/or chemotherapy. Sphingosine 1-phosphate (S1P) is a bioactive lipid that participates in all the steps of oncogenesis including tumor cell proliferation, survival, migration, invasion, and metastatic spread. The S1P-producing enzymes sphingosine kinases 1 and 2 (SK1 and SK2), and the S1P degrading enzyme

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… Fingolimod safety in combination with radiation and temozolomide was evaluated in a phase I clinical trial for newly diagnosed patients with high-grade glioma ( NCT02490930 ). …

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op