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Whole abdominopelvic intensity-modulated radiation therapy for desmoplastic small round cell tumor after surgery.

PURPOSE: Desmoplastic small round cell tumor (DSCRT) is an uncommon pediatric tumor with a poor prognosis. Aggressive multimodality therapy is the current treatment approach; however. treatment toxicity is of concern. We report our results with whole abdominopelvic intensity-modulated radiation therapy (WAP-IMRT) as a component of multimodality therapy for DSCRT at a single institution. MATERIALS/METHODS: Medical records of all patients with DSCRT who received WAP-IMRT as part of definitive treatment at MD Anderson (2006-2010) were identified and reviewed. RESULTS: Eight patients with DSRCT

Chemoradiation for High-grade Neuroendocrine Carcinoma of the Rectum and Anal Canal.

OBJECTIVES: We evaluated outcomes in patients with high-grade neuroendocrine (HGNE) carcinoma of the anorectum treated with pelvic chemoradiation. MATERIALS AND METHODS: Between January 1, 2000 and February 17, 2013, 10 patients were confirmed to have HGNE carcinoma of the rectum or anal canal and treated with pelvic chemoradiation (radiation dose ≥45 Gy). Overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and patterns of failure were evaluated. RESULTS: Eight had pure HGNE carcinoma and 2 had HGNE carcinoma with minor component of adenocarcinoma. Median age

Nanotechnology-Driven Cancer Therapies for Precision Oncology: Advances and Clinical Outlook.

Cancer continues to pose a global health challenge, with conventional therapies often limited by non-specific toxicity, drug resistance, and an inadequate therapeutic index. Nanotechnology offers transformative opportunities by enabling targeted drug delivery, improved pharmacokinetics, and integrated diagnostic-therapeutic platforms (termed nanotheranostics). This review highlights key nanocarrier systems including liposomes, polymeric nanoparticles, dendrimers, inorganic nanostructures, carbon-based materials, extracellular vesicles, and hybrid platforms with a focus on human studies and cli

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… (C) Time-to-onset distribution stratified by sex. 150 CRLX101 (Cyclodextrin-Polymer Camptothecin Conjugate) In a first-in-human phase 1/2a clinical study, CRLX101 (a cyclodextrin-polymer conjugate of camptothecin) designed as a NP approximately 30–40 nm in diameter was evaluated for safety, pharmacokinetics … Pharmacokinetic analysis revealed prolonged systemic exposure to both polymer-conjugated and unconjugated camptothecin, with dose-proportional plasma concentrations. …

Biosynthesis of anticancer phytochemical compounds and their chemistry.

Cancer is a severe health issue, and cancer cases are rising yearly. New anticancer drugs have been developed as our understanding of the molecular mechanisms behind diverse solid tumors, and metastatic malignancies have increased. Plant-derived phytochemical compounds target different oncogenes, tumor suppressor genes, protein channels, immune cells, protein channels, and pumps, which have attracted much attention for treating cancer in preclinical studies. Despite the anticancer capabilities of these phytochemical compounds, systemic toxicity, medication resistance, and limited absorption re

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… In India, camptothecin is extracted from the tree Nothapodytes foetida , and this heterologous expression system can provide an alternative approach to enhancing camptothecin production ( Singh et al., 2020 ). … This study showed that chitin-treated cell suspension culture had a higher amount of camptothecin with 11.48-fold increases in camptothecin level ( Keshavan et al., 2022 ). …

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals

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… A final subgroup within the category of drugs affecting cellular DNA consists of those derived from camptothecins, which are natural compounds originating from camptothecin, an alkaloid found in the Chinese tree Camptotheca acuminata [ 133 ]. … An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J. Nat. Prod. 2009;72:2–7. doi: 10.1021/np800455b. 134. Pommier Y. Camptothecins and topoisomerase I: A foot in the door. …

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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… Noncleavable | HER2 | IgG1 | HER2+ metastatic breast cancer previously treated with trastuzumab and a taxane (2013); HER2+ early breast cancer after neoadjuvant taxane & trastuzumab‐based treatment (2019) | FDA (2013, 2019) Fam‐trastuzumab deruxtecan‐nxki/Enhertu® (AstraZeneca/Daiichi Sankyo) | DXd (Camptothecin … | Cleavable (Sulfonyl pyrimidine‐CL2A‐carbonate) | 3 | NSCLC | NCT05351788 IBI354 | HER2 | Undisclosed | Camptothecin | Undisclosed | 1 | Locally advanced unresectable or metastatic solid tumors | NCT05636215 TQB2103 | Claudin‐18.2 | DDDXD | TOP1i | Cleavable | 1 | ADVANCED malignant neoplasm | NCT05867563 …

Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.

PURPOSE: We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients. PATIENTS AND METHODS: Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m(2) (n = 20) and 350 mg/m(2) (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (AN

Development of a chemoresistant orthotopic human nonsmall cell lung carcinoma model in nude mice: analyses of tumor heterogenity in relation to the immunohistochemical levels of expression of cyclooxygenase-2, ornithine decarboxylase, lung-related resistance protein, prostaglandin E synthetase, and glutathione-S-transferase-alpha (GST)-alpha, GST-mu, and GST-pi.

BACKGROUND: Nonsmall cell lung carcinomas (NSCLCs) are associated with very dismal prognoses, and adjuvant chemotherapy, including irinotecan, taxanes, platin, and vinca alkaloid derivatives, offer patients only slight clinical benefits. Part of the chemoresistance of NSCLC results from the expression in NSCLC cells of a very large set of endogenous proteins, which antagonize chemotherapy-mediated attacks on these tumor cells. METHODS: The authors set up an orthotopic model of a human NSCLC by grafting A549 cells into the lungs of nude mice. They tried treating these A549 NSCLC orthotopic xen

Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia.

Rubitecan [Orathecin, 9-nitrocamptothecin, 9NC, RFS 2000] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. One of the major benefits of rubitecan is that it can be administered in an outpatient setting, so patients can be treated in their homes. Rubitecan was isolated by the Stehlin Foundation in the US. SuperGen is currently awaiting regulatory approval in the US and the EU for rubitecan in the t…

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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… In this context, Lin et al. [ 57 ] developed liposomes functionalized with α-melanocyte-stimulating hormone (α-MSH) and loading camptothecin ( Figure 14 ) ( Table 3 , C14). … Camptothecin-Loaded Liposomes with α-Melanocyte-Stimulating Hormone Enhance Cytotoxicity Toward and Cellular Uptake by Melanomas: An Application of Nanomedicine on Natural Product. J. Tradit. Complement. Med. 2013;3:102–109. doi: 10.4103/2225-4110.110423. 58. …

Tumor Targeting with Peptide-Drug Conjugates: Showcasing Key Progress and Hurdles.

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs' small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circul

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… An example is a camptothecin-based self-assembling prodrug (SAPD) hydrogel, which transforms into supramolecular filaments upon contact with brain tissue. … Camptothecin-based anticancer therapies and strategies to improve their therapeutic index. Cancers . 2025;17(6):1032. doi: 10.3390/cancers17061032 69. Perra M, Castangia I, Aroffu M, et al. …

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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… Yet again, docetaxel was more efficient than camptothecin in inhibiting SK1 activity and increasing ceramide/S1P content in a murine orthotopic model of PC-3/GFP cells [ 59 ]. … A few years later, it was demonstrated that the selective inhibition of SK1 activity by B-5354c sensitized LNCaP and PC-3 cells to camptothecin-induced and docetaxel-induced apoptosis, respectively [ 61 , 98 ]. …

Poly(ethylene glycol)-Prodrug Conjugates: Concept, Design, and Applications.

Poly(ethylene glycol) (PEG) is the most widely used polymer in delivering anticancer drugs clinically. PEGylation (i.e., the covalent attachment of PEG) of peptides proteins, drugs, and bioactives is known to enhance the aqueous solubility of hydrophobic drugs, prolong circulation time, minimize nonspecific uptake, and achieve specific tumor targetability through the enhanced permeability and retention effect. Numerous PEG-based therapeutics have been developed, and several have received market approval. A vast amount of clinical experience has been gained which has helped to design PEG prodru

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… PEG-Drug Conjugates PEG low-molecular-weight drug conjugates that entered the clinical trials are mostly from the camptothecin (CPT) family, namely, camptothecin itself, SN38, and irinotecan ( Table 1 ). … Prothecan (PEG-Camptothecin) Pegamotecan is a product of Enzon Pharmaceuticals, Inc. which is PEG prodrug of the DNA damaging agent. …

Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

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… This conjugate is in clinical trials for the treatment of advanced solid tumors in patients with brain metastases. 148 A number of cancer-targeting PDCs, such as camptothecin–somatostatin conjugate, 149 camptothecin–bombesin conjugate, 150 , 151 H2009.1 peptide-polyglutamic acid–doxorubicin conjugate … Synthesis and antiproliferative activities of conjugates of paclitaxel and camptothecin with a cyclic cell-penetrating peptide. Molecules . 2019;24(7):E1427. doi: 10.3390/molecules24071427 132. Li W, Jia H, Wang J, et al. …

Convergent targeting of FUNDC1-dependent mitophagy sensitises and overcomes resistance to EGFR inhibition.

Combination therapies are critical for enhancing and prolonging the efficacy of EGFR inhibitors. Here, we uncover FUNDC1-dependent mitophagy as a key protective mechanism in EGFR-mutant non-small cell lung cancer (NSCLC). We discover that nitidine, a bioactive component of the traditional Xihuang Pill formulation, synergises with the EGFR inhibitor osimertinib. Mechanistically, nitidine and osimertinib synergistically disrupt FUNDC1-mediated mitophagy, leading to mitochondrial dysfunction and accumulation of reactive oxygen species in EGFR-mutant NSCLC. We further show that both osimertinib an

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… Among these, three monomeric compounds—camptothecin (C32), hypericin (C48) and nitidine (C59)—demonstrated potent cytotoxicity in PC‐9 cells, with nitidine showing the highest efficacy (Figure 2C ). … (D) Clonogenic assay of PC‐9 and NCI‐H1975 cells treated with varying concentrations of camptothecin (C32), hypericin (C48) or nitidine (C59). (E) Inhibition efficacy of PC‐9 and NCI‐H1975 cells following treatment with DMSO or varying concentrations of camptothecin, hypericin or nitidine. …

Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer.

Aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) is a second-line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty-two patients with metastatic colorectal cancer received aflibercept (4 mg/kg) plus FOLFIRI every 2 weeks. Seventy-eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor-stroma

Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance.

The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is commonly overexpressed in cancers and is implicated in the development of chemoresistance. The use of drugs inhibiting MGMT has been hindered by their haematologic toxicity and inefficiency. As a different strategy to inhibit MGMT we investigated cellular regulators of MGMT expression in multiple cancers. Here we show a significant correlation between Wnt signalling and MGMT expression in cancers with different origin and confirm the findings by bioinformatic analysis and immunofluorescence. We demonstrate Wnt-dependent MGM

RTP801 is elevated in Parkinson brain substantia nigral neurons and mediates death in cellular models of Parkinson's disease by a mechanism involving mammalian target of rapamycin inactivation.

The molecules underlying neuron loss in Parkinson's disease (PD) are essentially unknown, and current therapies focus on diminishing symptoms rather than preventing neuron death. We identified RTP801 as a gene whose transcripts were highly induced in a cellular model of PD in which death of neuronal catecholaminergic PC12 cells was triggered by the PD mimetic 6-OHDA. Here, we find that RTP801 protein is also induced in this and additional cellular and animal PD models. To assess the relevance of these observations to PD, we used immunohistochemistry to compare RTP801 expression in postmortem b

Mesoporous Silica Nanoparticles as Drug Delivery Vehicles in Cancer.

Even though cancer treatment has improved over the recent decades, still more specific and effective treatment concepts are mandatory. Surgical removal is not always possible, metastases are challenging and chemo- and radiotherapy can not only have severe side-effects but also resistances may occur. To cope with these challenges more efficient therapies with fewer side-effects are required. One promising approach is the use of drug delivery vehicles. Here, mesoporous silica nanoparticles (MSN) are discussed as biodegradable drug carrier to improve efficacy and reduce side-effects. MSN excellen

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… Using a biomolecule activated system, Mondragón et al. encapsulated camptothecin in MSN with a protease cleavable ε-poly- l -lysine and in human cervix epitheloid carcinoma cells viability was reduced after camptothecin-loaded nanoparticle incubation [ 73 ]. … Furthermore, camptothecin-loaded MSN reduced tumor size faster and greater after in total 18 intraperitoneal injections over nine weeks. Also, hematology profiling suggested reduced toxicity of camptothecin-loaded MSN compared to the free drug [ 40 ]. …

Nanotechnology in Prostate Cancer: PSMA-Targeted Nanoplatforms, TME-Responsive Therapy, Immunomodulation, and Clinical Translation Challenges.

The field of nanotechnology has demonstrated considerable potential in the diagnosis and treatment of prostate cancer, particularly through the use of prostate-specific membrane antigen (PSMA)-targeted platforms and tumor microenvironment (TME)-responsive systems. In the context of diagnosis, nanoparticle-based molecular imaging probes have been shown to enhance detection sensitivity and specificity. These probes include superparamagnetic iron oxide, which is utilized in magnetic resonance imaging, and near-infrared fluorescent nanomicelles. Additionally, nanostructured liquid biopsy systems h

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… These properties render them well-suited for the delivery of chemotherapeutic agents, nucleic acids, or imaging agents. 83 , 84 For instance, PAMAM-based carriers loaded with camptothecin and conjugated with PSMA-targeting ligands have exhibited remarkable therapeutic efficacy in prostate cancer models … CRLX101, another nanomedicine, is a camptothecin-nanomedicine conjugate based on a cyclodextrin-polyethylene glycol polymer. The original design of the study was to reverse acquired resistance to enzalutamide by downregulating HIF-1α. …