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Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.

Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, pr

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… Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab. Clin. Color. Cancer. 2019;18:e370–e384. doi: 10.1016/j.clcc.2019.07.007. 36. …

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

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… Similarly, extensively studied enzyme/prodrug systems included cytosine deaminase (CD) combined with 5-fluorocytosine (5-FC) and carboxylesterase with the prodrug CPT-11 (irinotecan) for the treatment of colon cancer, osteosarcoma [132] or glioblastoma and brain stem glioma, respectively [133] . …

The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment.

Glioblastoma is the most common and aggressive brain tumour in adults, and despite ongoing efforts, effective treatment remains limited. Standard therapies often face challenges because of the tumour's specific biology, its aggressive nature, and the presence of certain physiological barriers in the brain that impede chemotherapeutics from reaching their target. Emerging research in circadian biology highlights the role of the internal circadian clock in tumour progression and treatment response. Evidence suggests that aligning therapy to patients' chronotypes could potentially improve treatme

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… Other agents used include nitrosourea, gefitinib, aflibercept, irinotecan, procarbazine, and vincristine (PCV) [ 10 , 21 ]. However, these drugs exhibit low bioavailability, poor pharmacokinetics, and cause brain tissue damage [ 11 ]. 4. …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

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… was 44%, which is higher than the ORR in patients with advanced pancreatic ductal adenocarcinoma after first‐line treatment with gemcitabine and nabpaclitaxel (34.4%). 145 , 146 Additionally, it is worth noticing that the ORR obtained in this trial is greater than the ORR for FOLFIRINOX (oxaliplatin, irinotecan …

Mechanisms and Functions of γδ T Cells in Tumor Cell Recognition.

γδ T cells are among the first line of defense in the immune system, playing a crucial role in bridging innate and adaptive immunity. Although γδ T cells are crucial for tumor immune surveillance, the complete mechanism by which γδ T cell receptors identify molecular targets in target cells remains unknown. Target cells can produce phosphoantigens (PAgs) via the mevalonate pathway or the methylerythritol phosphate pathway. The BTN3A1-BTN2A1 complex undergoes conformational changes in its extracellular domains upon binding to PAgs, leading to Vγ9Vδ2 T cell recognition. However, the structural b

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… NCT05400603 | Ex Vivo Expanded Allogeneic γδ T cells in Combination with Dinutuximab, Temozolomide, Irinotecan, and Zoledronate | Neuroblastoma Refractory Neuroblastoma Relapsed Neuroblastoma Relapsed Osteosarcoma Refractory Osteosarcoma | I | Recruiting (Study Completion December 2025). …

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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… It is also used in combination with irinotecan to treat cancers with overexpression of EGFR. It works by competitively binding the extracellular second L2 domain of EGFR, thus blocking the ligand interaction and downstream signaling. …

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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… The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells. Int. J. Oncol. 2009;35:1463–1471. doi: 10.3892/ijo_00000465. 125. Ling L.-U., Tan K.-B., Chiu G.N.C. …

Gamma/delta T cells as cellular vehicles for anti-tumor immunity.

Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied in these therapies have proven efficacy but are confined almost exclusively to autologous use. When infused into patients with mismatched human leukocyte antigen, αβ T cells recognize tissues of such patients as foreign and elicit devastating graft-versus-host disease. Therefore, one way to overcome this challenge is to use naturally allogeneic immune cell typ

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… NCT05400603 | Recruiting | γδ T cells in combination with dinutuximab, temozolomide, irinotecan and zoledronate (Vδ2 T cells) | Allogeneic | PB | nil | 1 | R/r neuroblastoma (pediatric) | No published results. …

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making dia

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… Second-line treatments include irinotecan-cisplatin-mitomycin, cisplatin-gemcitabine, and oxaliplatin-raltitrexed ( 93 ). Radiotherapy Radiation is utilized to treat MPM patients. …

Anticancer natural products from the Middle East and North Africa: biodiversity, mechanisms, and translational challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, imposing substantial clinical, societal, and economic burdens. Despite major advances in surgical oncology, systemic chemotherapy, radiation therapy, molecularly targeted therapeutics, and immune checkpoint inhibition, contemporary cancer treatment remains constrained by dose-limiting toxicities, intratumoral and intertumoral heterogeneity, and the inexorable emergence of multifaceted drug resistance mechanisms. These persistent therapeutic challenges have reinstated interest in natural products (NPs) as evolutionar

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… These include camptothecin and its derivatives (topotecan, irinotecan), which form stabilized complexes with DNA and topoisomerase I ( 94 ), preventing DNA religation and inducing double-strand breaks ( 37 , 49 ). …

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

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… Irinotecan (IRI) is widely used in chemotherapy regimens for metastatic colorectal cancer (mCRC), but its efficacy is limited by acquired resistance [ 106 ] . Chen et al. analyzed the single-cell metabolomics of IRI-resistant HCT-116 cells using single-probe single-cell MS (SCMS) [ 106 ] . …

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

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… For instance, RES serves as an effective chemical sensitizer for colorectal cancer cells, enhancing their responsiveness to chemotherapeutic drugs such as irinotecan and 5‐FU, among others [ 212 ]. …

A new era of cancer immunotherapy: vaccines and miRNAs.

Cancer immunotherapy has transformed the treatment landscape, introducing new strategies to fight various types of cancer. This review examines the important role of vaccines in cancer therapy, focusing on recent advancements such as dendritic cell vaccines, mRNA vaccines, and viral vector-based approaches. The relationship between cancer and the immune system highlights the importance of vaccines as therapeutic tools. The discussion covers tumor cell and dendritic cell vaccines, protein/peptide vaccines, and nucleic acid vaccines (including DNA, RNA, or viral vector-based), with a focus on th

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… Other drugs associated with cardiotoxicity include oxaliplatin, carboplatin, cisplatin, ifosfamide, mitomycin C, bleomycin, methotrexate, vinca alkaloids, bendamustine, nitrosoureas, melphalan, gemcitabine, capecitabine, pemetrexed, and irinotecan. …

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

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… Among them are doxorubicin (Doxil ® , 1995 and Myocet ® , 2000), danourobicin (DaunoXome ® , 1996), cytarabine (Depocyt ® , 1999), mifamurtide (Mepact ® , 2004), vincristine (Marquibo ® , 2012), and irinotecan (Onivyde TM , 2015). …

Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly

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… Treatment of metastatic pancreatic cancer relies on chemotherapeutic regimens, with FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane) plus gemcitabine as first-line therapies, and combinations of gemcitabine plus …

Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges.

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics canc

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… that the sales of the top approved nanomedicine products were brought in $950 M (Abraxane ® ; paclitaxel protein-bound nanoparticles injection suspension), $275 M (Depocyte ® ; Cytarabine liposome injection), $252 M (Doxil ® /Caelyx ® ; doxorubicin-loaded PEGylated liposomes), and $122 M (ONIVYD ® ; irinotecan …

Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.

Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, h

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… Curcumin may also interfere with irinotecan absorption and efficacy ( Johnson and Mukhtar, 2007 ). Interactions Turmeric’s beneficial effects are undeniable; however, its consumption may interact with certain drugs and lead to several risks. …

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research-practice gaps, challenges, and insights.

To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune-based therapeutic modalities of anticancer

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… Farydak (Panobinostat) | 2015 | HDAC | Multiple myeloma | SR47,50,96,97 Ninlaro (Ixazomib) | 2015 | Beta 5 subunit of the 20S proteasome | Multiple myeloma | SR98 Lonsurf (Trifluridine and tipiracil) | 2015 | Nucleoside metabolic and thymidine phosphorylase | Metastatic colorectal cancer | SR99 Onivyde(Irinotecan … context of cancer therapies, and the results showed that circadian timing largely modifies the extent of toxicity of 40 anticancer drugs among agents in all pharmacological classes in rodents 328 and humans. 338 , 347 Doxorubicin (DOX), cisplatin, 5‐fluorouracil (5‐FU) and 5‐fluoro‐2′‐deoxyuridine, irinotecan …

Optimizing treatment efficacy and fertility preservation in patients undergoing hematopoietic stem cell transplantation: A narrative review of ovarian shielding with total-body irradiation or treosulfan-based conditioning regimens.

BackgroundPediatric and adolescent/young adult (AYA) patients with hematologic malignancies often require hematopoietic stem cell transplantation (HSCT) using conditioning regimens that pose high risks for gonadal toxicity. Traditional protocols, including total body irradiation (TBI) and busulfan-based regimens, can impair fertility. This review explores the potential of gonadal shielding during TBI and treosulfan-based conditioning as strategies to optimize treatment efficacy while preserving fertility.MethodsA PubMed search up to February 2025 was performed for English, peer-reviewed articl

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… fludarabine) Tubulin‐binding agents/vinca alkaloids (vincristine and vinblastine) Topoisomerase inhibitors (etoposide) Antitumor antibiotics (bleomycin, dactinomycin, and mitomycin C) Unknown risk | Antimetabolites (fluorouracil and thioguanine) Taxanes (paclitaxel and docetaxel) Topoisomerase inhibitors (irinotecan …