Recent advances in targeted strategies for triple-negative breast cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 28, 2023

Triple-negative breast cancer (TNBC), a highly aggressive subtype of cancer, negatively expresses estrogen receptor, progesterone and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is main form treatment for patients with TNBC, effectiveness TNBC still limited. The search more effective therapies urgent. Multiple targeted therapeutic strategies have emerged according to specific molecules signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, Notch poly ADP-ribose polymerase antibody-drug conjugates. Moreover, immune checkpoint example, pembrolizumab, atezolizumab, durvalumab, are widely explored clinic. We summarize recent advances therapy immunotherapy aim serving as reference development individualized future.

Language: Английский

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Peptide-drug conjugates: A new paradigm for targeted cancer therapy

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 265, P. 116119 - 116119

Published: Jan. 1, 2024

Language: Английский

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Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(2), P. 309 - 334

Published: Jan. 24, 2024

The emergence of peptide–drug conjugates (PDCs) that utilize target-oriented peptide moieties as carriers cytotoxic payloads, interconnected with various cleavable/noncleavable linkers, resulted in the key-foundation new era targeted therapeutics. They are capable retaining integrity blood circulatory system well releasing drugs at tumor microenvironment. Other valuable advantages specificity and selectivity toward targeted-receptors, higher penetration ability, drug-loading capacity, making them a suitable candidate to play their vital role promising carrier agents. In this review, we summarized types cell-targeting (CTPs) cell-penetrating peptides (CPPs) have broad applications advancement drug-delivery systems (DDS). Moreover, techniques overcome limitations peptide-chemistry for extensive implementation construct PDCs. Besides this, diversified breakthrough linker chemistry, ample knowledge payloads used PDCs recent years, mechanism action was critically discussed. principal aim is provide scattered one place help researchers understand pinching knots science PDC development, also progression bright future novel theranostics clinical practice.

Language: Английский

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Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.

Language: Английский

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Development of antibody‐drug conjugates in cancer: Overview and prospects

Cancer Communications, Journal Year: 2023, Volume and Issue: 44(1), P. 3 - 22

Published: Dec. 30, 2023

Abstract In recent years, remarkable breakthroughs have been reported on antibody‐drug conjugates (ADCs), with 15 ADCs successfully entering the market over past decade. This substantial development has positioned as one of fastest‐growing domains in realm anticancer drugs, demonstrating their efficacy treating a wide array malignancies. Nonetheless, there is still an unmet clinical need for wider application, better efficacy, and fewer side effects ADCs. An ADC generally comprises antibody, linker payload, combination profound drug structure, pharmacokinetic profile efficacy. Hence, optimization key components provides opportunity to develop higher potency effects. this review, we comprehensively reviewed current prospects ADC, provided analysis marketed ongoing pipelines globally well China, highlighted several platforms technologies specific different pharmaceutical enterprises biotech companies, also discussed new related technologies, possibility next‐generation directions research.

Language: Английский

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Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 22, 2024

Abstract Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor attracted increasing attention. stem cells (CSCs), small subset with self-renewal differentiation capacities, are resistant to traditional therapies such radiotherapy chemotherapy. Recently, CSCs have been proven be driving immunotherapy. However, mutual interactions between cancer niche immune largely uncharacterized. In this review, we focus on CSCs, CSC-immune cell CSC-based Colorectal characterized by robust expression surface markers CD44, CD133 Lgr5; hyperactivation stemness-related signaling pathways, Wnt/β-catenin, Hippo/Yap1, Jak/Stat Notch pathways; disordered epigenetic modifications, including DNA methylation, histone modification, chromatin remodeling, noncoding RNA action. Moreover, express abnormal levels immune-related genes MHC checkpoint molecules mutually interact multiple tumorigenesis-related processes, initiation, maintenance, metastasis drug resistance. To date, many targeting evaluated, monoclonal antibodies, antibody‒drug conjugates, bispecific vaccines adoptive therapy, molecule inhibitors. With development CSC-/niche-targeting technology, well integration multidisciplinary studies, novel that eliminate reverse their immunosuppressive microenvironment expected developed for solid tumors, cancer.

Language: Английский

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Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: March 1, 2024

Abstract A drug conjugate consists of a cytotoxic bound via linker to targeted ligand, allowing the delivery one or more tumor sites. This approach simultaneously reduces toxicity and increases efficacy, with powerful combination efficient killing precise targeting. Antibody‒drug conjugates (ADCs) are best-known type conjugate, combining specificity antibodies cytotoxicity chemotherapeutic drugs reduce adverse reactions by preferentially targeting payload tumor. The structure ADCs has also provided inspiration for development additional conjugates. In recent years, such as ADCs, peptide‒drug (PDCs) radionuclide (RDCs) have been approved Food Drug Administration (FDA). scope application expanding, including therapy delivery, variety new conjugation technology concepts emerged. Additionally, technology-based developed in industry. addition chemotherapy, immunotherapy, undergone continuous made significant progress treating lung cancer offering promising strategy treatment this disease. review, we discuss advances use treatment, structure-based design, mechanisms action, clinical trials, side effects. Furthermore, challenges, potential approaches future prospects presented.

Language: Английский

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Engineering peptide drug therapeutics through chemical conjugation and implication in clinics

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(6), P. 2420 - 2471

Published: May 5, 2024

The development of peptide drugs has made tremendous progress in the past few decades because advancements modification chemistry and analytical technologies. novel-designed have been modified through various biochemical methods with improved diagnostic, therapeutic, drug-delivery strategies. Researchers found it a helping hand to overcome inherent limitations peptides bring continued their applications. Furthermore, emergence peptide-drug conjugates (PDCs)-utilizes target-oriented moieties as vehicle for cytotoxic payloads via conjugation cleavable chemical agents, resulting key foundation new era targeted drugs. This review summarizes classifications drugs, suitable strategies improve ADME (adsorption, distribution, metabolism, excretion) features recent (2015-early 2024) progress/achievements peptide-based drug delivery systems well fruitful implication preclinical clinical studies. we also summarized brief description other types PDCs, including peptide-MOF peptide-UCNP conjugates. principal aim is provide scattered diversified knowledge one place help researchers understand pinching knots science PDC toward bright future novel

Language: Английский

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Engineered Antibodies as Cancer Radiotheranostics

Advanced Science, Journal Year: 2024, Volume and Issue: 11(30)

Published: June 14, 2024

Radiotheranostics is a rapidly growing approach in personalized medicine, merging diagnostic imaging and targeted radiotherapy to allow for the precise detection treatment of diseases, notably cancer. Radiolabeled antibodies have become indispensable tools field cancer theranostics due their high specificity affinity cancer-associated antigens, which allows accurate targeting with minimal impact on surrounding healthy tissues, enhancing therapeutic efficacy while reducing side effects, immune-modulating ability, versatility flexibility engineering conjugation. However, there are inherent limitations using as platform radiopharmaceuticals natural activities within immune system, large size preventing effective tumor penetration, relatively long half-life concerns prolonged radioactivity exposure. Antibody can solve these challenges preserving many advantages immunoglobulin framework. In this review, goal give general overview antibody design radiotheranostics. Particularly, four ways that applied enhance radioimmunoconjugates: pharmacokinetics optimization, site-specific bioconjugation, modulation Fc interactions, bispecific construct creation discussed. The radionuclide choices designed conjugates conjugation techniques future directions conjugate innovation advancement also

Language: Английский

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Transcytosable Peptide-Paclitaxel Prodrug Nanoparticle for Targeted Treatment of Triple-Negative Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4646 - 4646

Published: Feb. 28, 2023

Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As key component in standard of TNBC, paclitaxel (PTX) effectively inhibits growth proliferation tumor cells. However, application PTX clinical limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, side effects. To counter these problems, we constructed novel conjugate based peptide-drug conjugates (PDCs) strategy. In this conjugate, fused peptide TAR consisting tumor-targeting peptide, A7R, cell-penetrating TAT, used modify PTX. After modification, named PTX-SM-TAR, which expected improve specificity penetrability at site. Depending hydrophilic hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles water solubility terms linkage, acid- esterase-sensitive ester bond was as linking bond, NPs could remain stable physiological environment, whereas be broken released A cell uptake assay showed that were receptor-targeting mediate endocytosis by binding NRP-1. The vascular barrier, transcellular migration, spheroids experiments exhibit great transvascular transport penetration ability. vivo experiments, higher antitumor effects than result, may overcome shortcomings present new transcytosable targeted delivery system treatment.

Language: Английский

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