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Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following th

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… These include alkylating agents such as lomustine and cisplatin; anthracyclines such as Doxorubicin; topoisomerase inhibitors such as Irinotecan; and plant alkaloids such as Vinblastine. …

Advancements in antibody-drug conjugates as cancer therapeutics.

Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, h

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… large B-cell lymphoma) | Protease-cleavable MC-VC-PAB | 3.4–3.5 | MMAE microtubule-disrupting agent | June 10, 2019 Gilead sciences Sacituzumab govitecan-hziy (Trodelvy) | TROP-2 (Metastatic triple-negative breast cancer) | CL2A (acid-labile) | 7–8 | SN-38 (Active metabolite of the anti-cancer drug irinotecan …

The Multifaceted Role of Annexin A1 in Colorectal Cancer: From Molecular Mechanisms to Predictive and Prognostic Implications.

Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, is considered a key modulator of cancer biology. Numerous pieces of evidence support its multifaceted involvement in tumor progression, metastatic dissemination, immune escape, and resistance to therapy in various malignancies, such as melanoma, along with liver, lung, and digestive tract tumors, including stomach and colorectal cancer (CRC). Although colon and rectal cancer (RC) exhibit overlapping characteristics, they are classified as separate clinical entities due to differences in tumor biology and therapy approaches.

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… Since the early 2000s, the first-line therapy for advanced CRC has consisted of a combination regimen, incorporating 5-FU/leucovorin with either oxaliplatin or irinotecan [ 162 ]. …

Antibody drug conjugates in the clinic.

Antibody-drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell-killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)-approved products and discussing over 500 active clinical trials investigating newer

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… Sacituzumab govitecan comprises a humanized anti‐TROP2 IgG1 antibody linked by a hydrolyzable hydrazone linker to SN‐38, a topoisomerase‐1 inhibitor and the active metabolite of irinotecan. …

Traditional and Complementary Medicine Use among Cancer Patients in Asian Countries: A Systematic Review and Meta-Analysis.

Globally, cancer patients frequently use T&CM during their treatment for various reasons. The primary concerns regarding the use of T&CM among cancer patients are the potential risks associated with interactions between pharmaceuticals and T&CM, as well as the risk of noncompliance with conventional cancer treatments. Despite the higher prevalence of T&CM use in Asia, driven by cultural, historical, and resource-related factors, no prior review has tried to estimate the prevalence and influencing factors of T&CM use and disclosure among cancer patients in this region. This study aims to examin

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… John’s wort on irinotecan metabolism. J. Natl. Cancer Inst. 2002;94:1247–1249. doi: 10.1093/jnci/94.16.1247. 19. Ambrosone C.B., Zirpoli G.R., Hutson A.D., McCann W.E., McCann S.E., Barlow W.E., Kelly K.M., Cannioto R., Sucheston-Campbell L.E., Hershman D.L., et al. …

JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies.

JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell proliferation, cell survival, apoptosis and hematopoiesis of myeloid and non-myeloid cells. Dysregulation of JAK/STAT signaling is reported in various immunological disorders, hematological and other solid malignancies through various oncogenic activation mutations in receptors, downstream mediators, and a

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… The second line regimen for GC therapeutics is irinotecan, docetaxel, and paclitaxel. …

Safety and Tolerability of Antibody-Drug Conjugates in Cancer.

Antibody-drug conjugates are monoclonal antibodies attached to biologically active drugs through chemical linkers that deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. Currently, there are about 110 ongoing studies implementing antibody-drug conjugates in the treatment of multiple human malignancies. Antibody-drug conjugates carry a feature of the specificity of a monoclonal antibody and the anti-neoplastic potential of a cytotoxin. The first antibody-drug conjugate was approved in 2001, and the field of antibody-drug

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… Sacituzumab Govitecan Sacituzumab govitecan (IMMU-132; Immunomedics, USA) is an anti-TROP-2 mAb conjugated with an active metabolite of irinotecan (SN-38) via a pH-sensitive linker. [ 62 ] TROP-2 is a receptor that can be found on many human cancer cells, such as of the breast, cervix, colon and rectum …

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution.

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amo

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… Indeed, tumor expression of GSTP1 does not predict the safety or efficacy of platinum-based chemotherapy regimen Folfirinox (leucovorin, fluorouracil, irinotecan, and oxaliplatin) in patients with pancreatic cancer [ 147 ]. …

New approaches for cancer treatment: antitumor drugs based on gene-targeted nucleic acids.

Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RNA (siRNA), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are t

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… Promising results were obtained in studies involving patients suffering from colon tumors and featuring the simultaneous use of An - giozyme with the Saltz therapeutic protocol (a combination of bolus 5-fluoruracil, leucovorin, and irinotecan). this ap- proach led to disease progression in only 12.5% …

E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.

Therapy resistance in gastrointestinal tumors remains a critical challenge in clinical oncology, severely compromising therapeutic efficacy and long-term patient survival. E3 ubiquitin ligases, as core enzymes involved in the protein ubiquitination process, have been demonstrated to play indispensable roles in regulating key biological processes in tumor cells, including DNA damage repair, cell cycle progression, apoptosis, cancer stem cell maintenance, and immune evasion. Additionally, E3 ligases are key regulators of resistance to multiple anticancer strategies, such as chemotherapy, radioth

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… Concurrently, NEDD4–1 and WWP2 enhance MRP1 (ABCC1)- and BCRP (ABCG2)-mediated efflux of platinum compounds and irinotecan, diminishing intracellular drug accumulation and promoting resistance ( 100 ). (3) HERC2 stabilizes BRCA1 to augment homologous recombination (HR) capacity, counteracting PARP inhibitor-induced …

Insights into the role of RNA m6A modification in the metabolic process and related diseases.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperati

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… Carboxylesterase 2 (CES2) plays important roles in lipid mobilization and chemosensitivity to irinotecan. …

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodru

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… This design enhanced the uptake and release of miR-200 and irinotecan into the SAS cells, effectively inducing apoptosis. Additionally, these peptides were specifically engineered to act as nanovectors for irinotecan and miR-200, thereby improving the accumulation of tumor-specific drugs. …

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis.

In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of can

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… In a Wistar rat model, co-treatment of irinotecan with THC led to decreased hepatic toxicity, which suggested a protective role of THC on liver injury during acute treatment [ 85 ]. …

Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characte

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… Through ligand-based virtual screening and biophysical methods, several promising compounds—including azelastine, belotecan, and irinotecan—have been identified as effective G4 binders with notable antiproliferative effects in breast cancer cell lines [ 148 ]. …

Human microbiomes in cancer development and therapy.

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy

Trial Watch: combination of tyrosine kinase inhibitors (TKIs) and immunotherapy.

The past decades witnessed the clinical employment of targeted therapies including but not limited to tyrosine kinase inhibitors (TKIs) that restrain a broad variety of pro-tumorigenic signals. TKIs can be categorized into (i) agents that directly target cancer cells, (ii) normalize angiogenesis or (iii) affect cells of the hematologic lineage. However, a clear distinction of TKIs based on this definition is limited by the fact that many TKIs designed to inhibit cancer cells have also effects on immune cells that are being discovered. Additionally, TKIs originally designed to target hematologi

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… | | CRC | Toripalimab (anti-PD-1) | Phase I NCT04819516 (+ ultrasound therapy); Phase I–II NCT03946917 ; Phase II NCT04483219 | | CRC HCC | anti-PD-1 | NCT05233358 (+ HAIC or TACE); Phase I–II NCT04110093 ; Phase II NCT05048017 | | CRC HCC | Camrelizumab (anti-PD-1) | Phase I–II NCT04446091 (± irinotecan …

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma.

Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosi

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… . | Metastatic breast cancer Onivyde™ (2015) | Irinotecan | DSPC:Chol, DSPE-PEG-2000 | i.v. | Metastatic adenocarcinoma of the pancreas Onpattro TM (2018) | Transthyretin-directed small interfering RNA | DSPC:Chol:DLin-MC3-DMA:DMPG-PEG-2000 | i.v. | Polyneuropathy of hereditary transthyretin-mediated …

Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

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… A phase 3 clinical trial to treat Ewing sarcoma patients studies the effect of Vigil (Gradalis, Carrollton, TX, USA) on the progression free survival of patients treated with Irinotecan (Camptosar) and Temozolomide ( NCT03495921 ). …

The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics".

Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well a

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… There are also therapeutic chemotherapy strategies based on combinations between different drugs for each cancer type [ 75 ]: for non-small cell lung cancer; combinations include cisplatin-associated compounds; for colon cancer 5-fluorouracil; leucovorin and irinotecan are used in combination; for breast …