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Molecular Delivery of Cytotoxic Agents via Integrin Activation.

Integrins are cell adhesion receptors overexpressed in tumor cells. A direct inhibition of integrins was investigated, but the best inhibitors performed poorly in clinical trials. A gained attention towards these receptors arouse because they could be target for a selective transport of cytotoxic agents. Several active-targeting systems have been developed to use integrins as a selective cell entrance for some antitumor agents. The aim of this review paper is to report on the most recent results on covalent conjugates between integrin ligands and antitumor drugs. Cytotoxic drugs thus conjugate

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

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… Platinum compounds bind to DNA and cause DNA damage, leading to tumor cell apoptosis as the main anti-tumor mechanism. Elevated nucleotide excision repair (NER) is an important mechanism by which cells develop platinum compound resistance. High levels of the ERCC-1 protein support efficient NER. … Li et al. [ 116 ] found that β-elemene decreased the expression of the ERCC-1 gene and protein in ovarian cancer cells, thus making cells more sensitive to platinum compounds [ 117 ] and inducing tumor cell apoptosis. 3.4.8. …

Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy; cause and effect?

AbstractCancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the pre

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… Platinum compounds Platinum compounds, including carboplatin, cisplatin, and oxaliplatin, form platinum adducts that promote cross linking that can alter nuclear DNA structure and synthesis, 22 , 23 as well as mitochondrial DNA, leading to oxidative stress. 9 , 17 As a class, they contribute to the … First, there is the acute syndrome (which appears to be unique to oxaliplatin among the platinum compounds), which occurs during or immediately after administration of oxaliplatin, is seen in the majority of patients (85%–95%), can be triggered by cold, is characterized by neuronal hyperexcitability, …

Canine Gastric Cancer: Current Treatment Approaches.

Human gastric cancer (GC) ranks as the fifth most prevalent cancer worldwide, and is the third leading cause of cancer-related death. The incidence of GC is lower in dogs than in humans, accounting for less than 1% of all canine malignancies. In recent years, efforts have been made to understand the pathogenesis of GC and in find an appropriate therapy to maximize curative results, such as adjuvant chemotherapy treatments in addition to surgery. Although surgery is the first-line treatment, it is associated with several complications. In terms of chemotherapeutic intervention, canine gastric c

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an ada

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… Mitochondria does not have DNA repair systems to repair mitochondrial DNA adducts produced by platinum compounds and the consequence is an impairment of mitochondrial and respiratory chain function [ 10 ]. … Some side effects of platinum compounds can be potentially dose-limiting, such as myelosuppression, nephrotoxicity, ototoxicity, and CIPN. The cumulative chronic CIPN is similar in all platinum compounds, with lower frequency and intensity in carboplatin. …

Development of Newly Synthesized Chromone Derivatives with High Tumor Specificity against Human Oral Squamous Cell Carcinoma.

Since many anticancer drugs show severe adverse effects such as mucositis, peripheral neurotoxicity, and extravasation, it was crucial to explore new compounds with much reduced adverse effects. Comprehensive investigation with human malignant and nonmalignant cells demonstrated that derivatives of chromone, back-bone structure of flavonoid, showed much higher tumor specificity as compared with three major polyphenols in the natural kingdom, such as lignin-carbohydrate complex, tannin, and flavonoid. A total 291 newly synthesized compounds of 17 groups (consisting of 12 chromones, 2 esters, an

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro.

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… Discussion During recent years, there has been a renewed interest in platinum compounds in the treatment of triple negative breast cancer (TNBC) patients [ 40 ]. …

Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps.

BackgroundCisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity, leading to progressive and irreversible sensorineural hearing loss in up to 93% of patients. Cisplatin generates reactive oxygen species (ROS) in the cochlea, activating apoptotic and necroptotic pathways that result in hair cell death. Inflammatory processes and nitrative stress also contribute to cochlear damage.MethodsThis literature review was conducted to explore the mechanisms underlying cisplatin-induced ototoxicity and evaluate protective strategies, including both current and emergin

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… The anticancer properties of platinum compounds are primarily attributed to their ability to form covalent adducts on DNA [ 34 , 35 ]. Antioxidants could potentially interfere with this mechanism, potentially reducing the drug’s efficacy. … Antioxidant Properties of trans-3,3’,5,5’-Tetrahydroxy-4’-Methoxystilbene Against Modification of a Variety of Biomolecules in Human Blood Cells Treated with Platinum Compounds. Nutrients. 2006;22:1202–1209. doi: 10.1016/j.nut.2006.06.010. 34. Bose R.N. …

Melittin, a honeybee venom derived peptide for the treatment of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction. Severe CIPN has been reported in around 5% of patients treated with single and up to 38% of patients treated with multiple chemotherapeutic agents. Present medications available for CIPN are the use of opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants, which are only marginally effective in treating neuropathic symptoms. In reality, symptom reappears after these drugs are discontinued. The pathogene

Revolutionizing ovarian cancer therapy by drug repositioning for accelerated and cost-effective treatments.

Drug repositioning, the practice of identifying novel applications for existing drugs beyond their originally intended medical indications, stands as a transformative strategy revolutionizing pharmaceutical productivity. In contrast to conventional drug development approaches, this innovative method has proven to be exceptionally effective. This is particularly relevant for cancer therapy, where the demand for groundbreaking treatments continues to grow. This review focuses on drug repositioning for ovarian cancer treatment, showcasing a comprehensive exploration grounded in thorough in vitro

Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer.

Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns relat

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

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… CTR1 is highly expressed on neuronal cells in the DRG, leading to efficient uptake of platinum compounds, likely explaining the toxicity [ 73 ]. Cisplatin-induced neuropathy is dose-dependent and usually follows a cumulative dose of 400 mg/m 2 or higher [ 48 ]. … Toxicity of platinum compounds Expert Opin. Pharmacother. 2003 4 889 901 10.1517/14656566.4.6.889 12783586 92. Moudi M. Go R. Yien C.Y. Nazre M. Vinca alkaloids Int. J. Prev. Med. 2013 4 1231 1235 24404355 PMC3883245 93. Andreyev J. …

Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting side effect of several antineoplastic drugs which significantly reduces patients' quality of life. Although different molecular mechanisms have been investigated, CIPN pathobiology has not been clarified yet. It has largely been recognized that Dorsal Root Ganglia are the main targets of chemotherapy and that the longest nerves are the most damaged, together with fast axonal transport. Indeed, this bidirectional cargo-specific transport has a pivotal role in neuronal function and its impairment is involved in several neurodeg

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… Platinum Compounds Platinum compounds are a family of several antineoplastic drugs all characterized by the presence of a Platinum (Pt) atom in their chemical structure. … Cisplatin Cisplatin ( cis -diamminedichloroplatinum(II)) is the first drug of the platinum compounds family entered in clinical practice, effectively used for the treatment of several tumors, such as ovarian, testicular, and small cell lung cancers [ 99 ]. …

Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).

BACKGROUND: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of diseases which are generally associated with poor prognosis. Up to now, no targeted treatment beyond anti-VEGF therapy has been approved for TNBC and cytotoxic agents remain the mainstay of treatment. Ixazomib is a selective and reversible inhibitor of the proteasome, which has been mainly investigated in the treatment of multiple myeloma. In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrat

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… These particular molecular features might be exploited in novel targeted approaches and simultaneously indicate potential overlapping strategies in the treatment of breast and ovarian cancers, with platinum compounds representing the major backbone of treatment for the latter. …

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.

N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potenti

Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies.

BackgroundPeripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy.MethodThe current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of

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… Some of the common agents which causes CIPN includes taxanes, vinca alkaloids, platinum compounds and also newer effective anticancer agents like bortezomib [ 26 ]. … However, 60% of incidence has been reported with the usage of taxanes, vinca alkaloids, platinum compounds and bortezomib. …

Recent advancement in the anticancer efficacy of the natural flavonoid scutellarin: a comprehensive review.

Scutellarin (SC), a natural flavonoid, has been expansively employed in treating innumerable inflammation-related diseases due to its antitumor, antiinflammatory, anticancer, and antioxidant potential. Scutellarin can inhibit significant inflammatory cell signaling pathways, comprisingPI3K/Akt, NF-κB, and MAPK, and while activating antioxidant-related pathways such as Nrf2 and ARE. Numerous reviews have outlined scutellarin's pharmacological effects and associated mechanisms in inflammation-related diseases. Several studies have elucidated the mechanisms of anticancer activity by inhibiting va

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… FIGURE 7 Combination of scutellarin and platinum compounds as potent therapeutic strategy. … Thus, the combination therapy of platinum compounds and SC has demonstrated efficacy in mitigating resistance to platinum compound treatment, highlighting the advancement and utilization of natural product-based formulations of platinum compounds as an innovative therapeutic approach to combat human …

Exportin 1 as a Therapeutic Target to Overcome Drug Resistance in Lung Cancer.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality, with therapeutic resistance continuing to limit long-term responses. Among emerging resistance mechanisms, dysregulation of nucleocytoplasmic transport has gained attention for its ability to inactivate tumor suppressor pathways. Exportin 1 (XPO1), the primary nuclear export protein, is frequently overexpressed in NSCLC and promotes the cytoplasmic mislocalization of proteins involved in cell cycle control, apoptosis, and DNA repair. This includes key regulators such as p53, FOXO, and RB, whose inactivati

Assessing the Therapeutic Role of Rehabilitation Programs in Chemotherapy-Induced Peripheral Neuropathy (CIPN)-A Scoping Review.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients' quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O'Malley's framework and Levac et al.'s refinements, was conducted to