Molecular targeted therapies for cutaneous squamous cell carcinoma: recent developments and clinical implications.

PubMed, Journal Year: 2024, Volume and Issue: 23, P. 300 - 334

Published: Jan. 1, 2024

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses significant threat to public health has high prevalence rate. Exposure ultraviolet radiation on the surface increases risk cSCC, especially in those with genetic syndromes like xerodermapigmentosum epidermolysis bullosa. Therefore, understanding molecular pathogenesis cSCC critical for developing personalized treatment approaches are effective cSCC. This article provides comprehensive overview current knowledge pathogenesis, emphasizing dysregulated signaling pathways significance profiling. Several limitations challenges associated conventional therapies, however, identified, stressing need novel therapeutic strategies. The further discusses targets approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway PI3K/AKT/mTOR as well emerging agents. manuscript explores resistance mechanisms molecularly targeted therapies proposes methods overcome them, including combination strategies, rational design, optimization. clinical implications patient outcomes molecular-targeted treatments assessed, response rates survival outcomes. management adverse events toxicities crucial requires careful monitoring control. paper future directions advancement research this area, difficulties constraints therapies.

Language: Английский

---

FEN1 Inhibition as a Potential Novel Targeted Therapy against Breast Cancer and the Prognostic Relevance of FEN1

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2110 - 2110

Published: Feb. 9, 2024

To improve breast cancer treatment and to enable new strategies for therapeutic resistance, targets are constantly being studied. Potential proteins of DNA repair replication genomic integrity, such as Flap Endonuclease 1 (FEN1). This study investigated the effects FEN1 inhibitor FEN1-IN-4 in combination with ionizing radiation on cell death, clonogenic survival, cycle, senescence, doubling time, double-strand breaks micronuclei cells, cells healthy skin fibroblasts. Furthermore, variation baseline level its influence prognosis was investigated. The lines show specific response patterns aspects studied have heterogeneous levels. has cytotoxic, cytostatic radiosensitizing effects, expressed through increasing death by apoptosis necrosis, G2M share, a reduced survival fraction. Nevertheless, some less affected cytotoxicity fibroblasts rather limited response. In vivo, high mRNA expression worsens patients. Due increased tissue, could represent tumor marker may serve potent agent personalized medicine targeted therapy.

Language: Английский

---

Establishment of a novel microfluidic co-culture system for simultaneous analysis of multiple indicators of gefitinib sensitivity in colorectal cancer cells

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(5)

Published: April 22, 2024

Language: Английский

---

Chemoradiotherapy and nanomedicine: Drug mechanisms and delivery systems

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2024, Volume and Issue: 16(4)

Published: July 1, 2024

Abstract Radiotherapy is an invaluable tool in the treatment of cancer. However, when used as a monotherapy, it fails to provide curative outcomes. Chemotherapy drugs are often included boost effects radiation. Key classes radiosensitizing include platinum compounds, anthracyclines, antimetabolites, taxanes, topoisomerase inhibitors, alkylating agents, and DNA damage repair inhibitors. Chemoradiotherapy suffers from not only systemic toxicities chemotherapy but also synergistic radiation toxicity well. It critical deliver molecules tumor cells while avoiding adjacent healthy tissues. Currently, nanomedicine provides avenue for specific delivery radiosensitizers. Nanoscale vehicles can be synthesized lipids, polymers, or inorganic materials. Additionally, encompasses stimuli responsive particles including prodrug formulation activation. Clinically, radiotherapy intertwined with approved DOXIL Abraxane. Though many challenges remain, ongoing progress evidences promising future both chemoradiotherapy. This article categorized under: Therapeutic Approaches Drug Discovery > Nanomedicine Oncologic Disease Cardiovascular Emerging Technologies

Language: Английский

---

Pt-Au Nanoparticles in Combination with Near-Infrared-Based Hyperthermia Increase the Temperature and Impact on the Viability and Immune Phenotype of Human Hepatocellular Carcinoma Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1574 - 1574

Published: Feb. 13, 2025

Near-infrared light (NIR)-responsive metal-based nanoparticles (NPs) could be used for tumour therapy. We examined how platinum (Pt), gold (Au), and core-shell Pt-Au NPs affect the viability of human hepatocellular carcinoma (HCC) cell lines (Hep3B, HepG2, Huh7D-12) alone in combination with NIR exposure. In addition, expression immune checkpoint molecules (ICMs) on cells was analysed. revealed that cytotoxicity programmed death induction Au toward HCC enhanced by 960 nm a different way. were only particles resulted an additional temperature increase up to 2 °C after NIR. Regarding phenotype, not all experienced changes phenotype. itself trigger alterations, while did significantly most ICMs, such as PD-L1, HVEM, CD70, ICOS-L, Ox40-L, TNFRSF9. The prominent ICMs HepG2 cells. conclude thermotherapeutic effect NP application beneficial multimodal therapy settings liver cancer selected patients.

Language: Английский

---

Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116668 - 116668

Published: May 2, 2024

The combination of radiation treatment and chemotherapy is currently the standard for management cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat with already increased tumor resistance drugs irradiation. One solutions we suggest improve primary course via enhancing radiosensitivity tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized (hIONPs, ∼20 nm), characterized it TEM, Infrared spectroscopy DLS. Then hIONPs cytotoxicity was assessed colon cells (XTT assay) cellular uptake analyzed X-ray fluorescence. Combination ionizing (IR) in vitro caused an increase G2/M arrest cell cycle, mitotic errors decrease survival (compared samples exposed IR separately). promising results were shown CT26-grafted BALB/C mice: intravenously administrated showed 20,8% T/C ratio (related non-treated mice), while single had no significant growth (72,4%). Non-guided magnets 57,9% T/C. This indicates that ultra-small size biocompatible molecule key successful nano-drug design, each case, delivery technologies need be improved when transferred vivo model.

Language: Английский

---

A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 16, 2024

Abstract Background Adenocarcinoma of the lung is most common type cancer, and it characterized by distinct cellular molecular features. It occurs when abnormal cells multiply out control form a tumor in outer region lungs. serious life-threatening condition that requires effective timely management to improve survival quality life patients. One challenges this cancer treatment finding optimal combination drugs can target genes or proteins are involved disease process. Method In article, we propose novel method recommend combinations trending its associated proteins/genes, using Graph Neural Network (GNN) under RAIN protocol. The protocol three-step framework consists of: 1) Applying graph neural networks drug passing messages between for managing act as potential targets disease; 2) Retrieving relevant articles with clinical trials include those proposed previous step Natural Language Processing (NLP). search queries “Adenocarcinoma lung”, “Gefitinib”, “Paclitaxel”, “Icotinib” searched context based databases NLP; 3) Analyzing network meta-analysis measure comparative efficacy combinations. Result We applied our dataset nodes edges represent network, where each node gene, edge p-value them. found recommends combining Gefitinib, Paclitaxel, Icotinib proteins/genes. reviewed expert opinions on these medications they support claim. also confirmed effectiveness genes. Conclusion Our promising approach help clinicians researchers find best options patients, provide insights into underlying mechanisms disease. Highlights Proposing medicinal compounds together adenocarcinoma achieved 0.002858 targeted proteins/genes 3-Leveraging GraphSAGE Suggesting an Optimal Drug Combinations. Figure

Language: Английский

---

Targeted Therapy with Polymeric Nanoparticles in PBRM1-Mutant Biliary Tract Cancers: Harnessing DNA Damage Repair Mechanisms

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 204, P. 104505 - 104505

Published: Sept. 8, 2024

Language: Английский

---

Advances in protein kinase drug discovery through targeting gatekeeper mutations

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(12), P. 1349 - 1366

Published: Oct. 9, 2023

Acquired resistance caused by gatekeeper mutations has become a major challenge for approved kinase inhibitors used in the clinic. Consequently, development of new-generation or degraders to overcome clinical an important research focus field.This review summarizes common druggable kinases and constantly evolving designed single double residues. Furthermore, authors provide their perspectives on medicinal chemistry strategies addressing with mutations.The suggest optimizing interact effectively residues, altering binding mode pocket avoid steric clashes, improving affinity target, utilizing protein degraders, developing combination therapy. These approaches have potential be effective overcoming due

Language: Английский

---

Strahlentherapie und molekular zielgerichtete Therapie – alles gezielt?

Deleted Journal, Journal Year: 2024, Volume and Issue: 30(10), P. 938 - 944

Published: May 9, 2024

Die gezielte Inhibition von DNA-Reparaturmechanismen und anderer intrazellulärer Signalkaskaden gilt als vielversprechendes Instrument zur lokalen Wirkungsverstärkung einer Strahlentherapie. Der EGFR-Antagonist Cetuximab ist bislang der einzige speziell in dieser Indikation zugelassene zielgerichtete Wirkstoff. Eine große Zahl an zielgerichteten Kombinationstherapien wird aktuell klinisch getestet. Inhibitoren verschiedener (ATM, ATR, DNA-PK, WEE1, PARP) sowie Antagonisten Apoptoseproteine (IAP) werden Kombination mit Strahlentherapie Phase-I- -II-Studien erprobt. Phase-III-Studien u. a. Radiochemotherapie des Kopf-Hals-Plattenepithelkarzinoms (HNSCC) zum IAP-Antagonisten Xevinapant durchgeführt, welcher Phase-II-Studie einen klaren Überlebensvorteil bei geringem Toxizitätsprofil erbrachte. Es liegen viele erfolgversprechende präklinische Daten Medikamenten hinsichtlich Strahlensensibilisierung Tumoren vor. Allerdings gestaltet sich die Übertragung präklinisch wirksamen Konzepten Klinik schwierig. Am weitesten fortgeschritten Phase-III-Studie zu Xevinapant, deren Ergebnisse 2024 erwartet werden. Strategien effektiveren Einsatz zielgerichteter Therapie könnten Erforschung Biomarkern Entwicklung innovativer Studienkonzepte sein.

---