Recent progress in the development of therapies targeting molecular factors in breast cancer DOI Creative Commons
Dominika Kunachowicz, Monika Birska,

Karolina Kłosowska

et al.

Farmacja Polska, Journal Year: 2024, Volume and Issue: 80(3), P. 189 - 204

Published: July 25, 2024

Skuteczne leczenie chorób nowotworowych nadal pozostaje ogromnym wyzwaniem dla współczesnej medycyny, szczególnie w obliczu wciąż wzrastającej zapadalności. U kobiet, najczęściej występującym i najbardziej śmiertelnym nowotworem złośliwym jest rak piersi (ang. breast cancer, BC). Nowotwory są zróżnicowane pod względem przebiegu odpowiedzi na leczenie, a ich heterogenność sprzyja rozwojowi lekooporności tworzeniu przerzutów. Co więcej, niska specyficzność leków stosowanych aktualnych schematach terapeutycznych powoduje działania niepożądane, znacząco obniżając jakość życia pacjentek. Dlatego, by efektywnie leczyć BC, należy opracować nowe strategie terapeutyczne o korzystniejszym profilu bezpieczeństwa wyższej selektywności. Podczas nowotworzenia, szybko dzielących się nieprawidłowych komórkach modyfikacji ulegają ścieżki przekazu sygnału, regulujące przebieg cyklu komórkowego, wzrost proliferację. Komórki nowotworowe syntetyzują określone czynniki molekularne – m.in. receptory, białka sygnałowe, transkrypcyjne zaangażowane progresję guza, podczas gdy prawidłowych występują one mniej licznie lub nie aktywne. te mogłyby służyć jako biologiczne punkty uchwytu nowoczesnych terapii różnych postaci BC. Takie terapie celowane, hamujące nowotworu poprzez zaburzanie funkcji specyficznych biocząsteczek odpowiedzialnych za jego progresję, podstawą strategii leczenia. Wśród korzyści, które niesie stosowanie, można wymienić skuteczności z jednoczesnym zmniejszeniem jej inwazyjności. Podkreśla to pilną potrzebę poszukiwania nowych punktów leków, realizowaną ramach licznych badań. Celem niniejszej pracy przedstawienie usystematyzowanie aktualnego stanu wiedzy temat czynników molekularnych Aby dokonać analizy tego zagadnienia, dokonano przeglądu artykułów naukowych baz danych Medline oraz Google Scholar obejmujących lata 2013-2024. Kwerendę bibliograficzną przeprowadzono okresie listopad 2023 luty 2024, pomocą następujących słów kluczowych: „nowotwór piersi” cancer), „cele molekularne” molecular targets), „leczenie nowotworów cancer treatment), „terapie celowane” targeted therapies), „inhibitory sygnalizacji” signaling inhibitors), „fibroblasty związane nowotworami” associated fibroblasts), „niekodujące RNA” non-coding RNA). Opisana metodyka pozwoliła odnalezienie aktualnych, wiarygodnych informacji ponad 300 oryginalnych przeglądowych, spośród których do przygotowania wybrano 60. Przytoczone wyniki badań przedklinicznych klinicznych wskazują, że hamowanie białek ścieżek sygnalizacyjnych stymulujących komórek słuszną strategią, otwierającą perspektywy doskonalenia przeciwnowotworowych tym leczenia agresywnych Na podstawie przewiduje się, wprowadzenie użytku klinicznego ukierunkowanych konkretne biocząsteczki, zwiększy skuteczność selektywność Publikacja poszerza obecną wiedzę postępów opracowywaniu celowanych kątem zastosowania nowotworach stanowi zestawienie aktualnej literatury przedmiotu języku polskim.

Chimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy DOI
Shaida Ouladan, Elias Orouji

Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Colorectal cancer (CRC) remains a major global health burden, being one of the most prevalent cancers with high mortality rates. Despite advances in conventional treatment modalities, patients metastatic CRC often face limited options and poor outcomes. Chimeric antigen receptor-T (CAR-T) cell therapy, initially successful hematologic malignancies, presents promising avenue for treating solid tumors, including CRC. This review explores potential CAR-T therapy by analyzing clinical trials highlighting prominent CRC-specific targets. We discuss challenges such as immunosuppressive microenvironment, tumor heterogeneity, physical barriers that limit efficacy. Emerging strategies, logic-gated dual-targeting cells, offer practical solutions to overcome these hurdles. Furthermore, we explore combination immune checkpoint inhibitors enhance T-cell persistence infiltration. As field continues evolve, therapies hold significant revolutionizing landscape

Language: Английский

Citations

0
Development of FAP-targeted theranostics discovered by next-generation sequencing-augmented mining of a novel immunized VNAR library DOI Creative Commons
Gihan S. Gunaratne, Joseph P. Gallant, Kendahl L. Ott

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Cancer-associated fibroblasts (CAFs) in the stroma of solid tumors promote an immunosuppressive tumor microenvironment (TME) that drives resistance to therapies. The expression protease fibroblast activation protein (FAP) on surface CAFs has made FAP a target for development therapies dampen immunosuppression. Relatively few biologics have been developed and none exploit unique engagement properties Variable New Antigen Receptors (VNARs) from shark antibodies. As smallest binding domain nature, VNARs cleverage geometries recognize epitopes conventional antibodies cannot. By directly immunizing nurse with FAP, we created large anti-FAP VNAR phage display library. This library allowed us identify suite through traditional biopanning also by silico approach did not require any prior affinity-based enrichment vitro . We investigated four VNAR-Fc fusion proteins theranostic found all recognized high affinity were rapidly internalized FAP-positive cells. result, constructs effective antibody-drug conjugates able localize xenografts vivo Our findings establish as versatile platform could yield innovative cancer targeting TME.

Language: Английский

Citations

0
Advances in engineered T cell immunotherapy for autoimmune and other non-oncological diseases DOI Creative Commons

Qiaolin Huang,

Xiaojian Zhu,

Yicheng Zhang

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 4, 2025

Abstract Adoptive immunotherapy using engineered T cells expressing chimeric antigen receptors has shown remarkable success in treating patients with hematological malignancies. However, realizing broader therapeutic applications of other diseases requires further exploration clinical investigations. In this review, we highlight recent advances the engineering non-oncology areas, including autoimmune and inflammatory diseases, infections, fibrosis, hemophilia, aging. Chimeric receptor good outcomes but many challenges remain improving its safety efficacy expanding application to treatment non-oncological diseases.

Language: Английский

Citations

0
Anlotinib may have a therapeutic effect on papillary craniopharyngiomas without the BRAFv600e mutation DOI Creative Commons
Yilamujiang Ainiwan,

H. B. Li,

Yongjia Zheng

et al.

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 3, 2025

Although successful treatment of papillary craniopharyngiomas (PCPs) with BRAFv600e inhibitors has been reported in clinical trials, studies have shown that approximately 10% PCPs lack the mutation and may not be significantly effective against these tumors. However, no focused specifically on BRAFv600e− PCPs. Spatial transcriptome sequencing was performed calcified PCP tissue to identify novel subtypes cells. The findings were validated via pathological methods 51 samples. Primary cells from patients BRAFv600e+ isolated then injected into brains nude mice stereotactic surgery establish a stable mouse model human-originated PCP. Model treated vemurafenib, BRAF inhibitor, anlotinib, an angiogenesis inhibitor. BRAFv600e−PCP anlotinib phase 1 trial. Changes tumors monitored methods, CT MRI. Most negative for mutation, confirmed vemurafenib significant therapeutic effect verified that, Two participated trial received therapy; their disappeared after 3 months therapy did recur within 24 follow-up stopping treatment. are characterized by calcification do respond inhibitor which effect.

Language: Английский

Citations

0
Enhanced efficacy of dual chimeric antigen receptor-T cells targeting programmed death-ligand 1 and cancer-associated fibroblasts in colorectal cancer in vitro DOI Open Access
Yang Gao, Chunxiong Luo,

Hua Yang

et al.

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 29 - 29

Published: March 6, 2025

Colorectal cancer (CRC) presents significant treatment challenges, including immune evasion and tumor microenvironment (TME) suppression. Chimeric antigen receptor (CAR) T-cell therapy has shown promise in hematologic malignancies, but its effectiveness against solid tumors is hampered by the detrimental effects of TME. This article aims to explore potential bispecific CAR T cells targeting programmed death-ligand 1 (PD-L1) cancer-associated fibroblasts (CAFs) CRC treatment. Dual-targeted CAR-T PD-L1 CAF were engineered using GV400 lentiviral vector. Programmed death-1 (PD-1)/nanobody (Nb) fibroblast activation protein (FAP)/Nb-encoding vectors generated, produced through a three-plasmid system 293T cells. Human peripheral blood mononuclear (PBMCs) separated, transduced with these vectors, then expanded. Functional characterization was performed enzyme-linked immunosorbent assay (ELISA), Western blot analysis, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, cell counting kit-8 (CCK-8) assay. Migration invasion assays conducted Transwell chambers assess ability FAP-PD-1/Nb migrate toward invade extracellular matrix. We developed dual-targeted incorporating Nbs, which continuously secreted PD-1/Nb. confirmed PD-1/Nb expression cells, no untreated (UTD) group (P < 0.01). Flow cytometry showed significantly higher cluster differentiation (CD)25 CD69 upon stimulation FAP-positive target compared other groups TUNEL, CCK-8 revealed that exhibited superior cytotoxicity proliferation inhibition HCT116 ELISA demonstrated increased interferon-gamma necrosis factor-alpha levels reduced interleukin-10 0.01), suggesting enhanced cytokine modulation antitumor immunity. Compared single-target UTD, notably Matrigel penetration Safety tests minimal normal PBMCs, indicating favorable safety. study successfully their activity immunomodulatory on novel therapeutic strategy established technology for CRC.

Language: Английский

Citations

0
scRNA-seq characterizing the heterogeneity of fibroblasts in breast cancer reveals a novel subtype SFRP4+ CAF that inhibits migration and predicts prognosis DOI Creative Commons
Lvwen Ning,

Chuntao Quan,

Yue Wang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 15, 2024

Introduction Cancer-associated fibroblasts (CAFs) are a diverse group of cells that significantly impact the tumor microenvironment and therapeutic responses in breast cancer (BC). Despite their importance, comprehensive profile CAFs BC remains to be fully elucidated. Methods To address this gap, we utilized single-cell RNA sequencing (scRNA-seq) delineate CAF landscape within 14 normal-tumor paired samples. We further corroborated our findings by analyzing several public datasets, thereby validating newly identified subtype. Additionally, conducted coculture experiments with assess functional implications Results Our scRNA-seq analysis unveiled eight distinct subtypes across five six adjacent normal tissue Notably, discovered novel subtype, designated as SFRP4+ CAFs, which was predominantly observed tissues. The presence substantiated two independent datasets spatial transcriptomics dataset. Functionally, were found impede cell migration epithelial-mesenchymal transition (EMT) process secreting SFRP4, modulating WNT signaling pathway. Furthermore, established elevated expression levels markers correlate improved survival outcomes patients, yet paradoxically, they predict diminished response neoadjuvant chemotherapy cases triple-negative cancer. Conclusion This investigation sheds light on heterogeneity introduces subtype hinders migration. discovery holds promise potential biomarker for refined prognostic assessment intervention BC.

Language: Английский

Citations

3
CAR-T Cell Therapy: Advances in Digestive system malignant tumors DOI Creative Commons

Nan Xu,

Zhonglin Wu,

Jun Pan

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 32(4), P. 200872 - 200872

Published: Sept. 10, 2024

Malignant tumors of the digestive system have had a notoriously dismal prognosis throughout history. Immunotherapy, radiotherapy, surgery, and chemotherapy are primary therapeutic approaches for cancers. The rate recurrence metastasis, nevertheless, remains elevated. As one immunotherapies, chimeric antigen receptor T cell (CAR-T) therapy has demonstrated promising antitumor effect in hematologic cancer. Despite undergoing numerous clinical trials, ineffective adverse effects CAR-T treatment cancers continue to impede its translation. It is necessary surmount restricted options targeting proteins, obstacles that infiltration into solid tumors, limited survival time

Language: Английский

Citations

2
Nano-enhanced immunity: A bibliometric analysis of nanoparticles in vaccine adjuvant research DOI Creative Commons
Manal Mohamed Elhassan Taha, Mohamed Yousif Ibrahim, Sivakumar S. Moni

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: Nov. 14, 2024

This study analyzed the growth, collaboration, citation trends, and emerging topics in nanoparticle-based vaccine adjuvant research (NVAR) from 1977 to 2023, using data Scopus database. The field showed a steady growth rate of 7.53% per year. Leading researchers Jaafari, M.R. Alving, C.R. contributed significantly field, with 24.22% publications 38.92% total citations coming United States. International collaboration was very strong, particularly between US, UK, Germany, China, France. Key include nanoparticles, immunotherapy, COVID-19, vaccines focus on SARS-CoV-2 malaria. Emerging adjuvants, mRNA, neutralizing antibodies. emphasizes importance ongoing interdisciplinary efforts advance NVAR.

Language: Английский

Citations

2
Clear Cell Renal Cell Carcinoma: A Test Bench for Investigating Tumor Complexity DOI Open Access
Claudia Manini, E. López-Anglada Fernández, Gorka Larrinaga

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 829 - 829

Published: Feb. 19, 2024

Clear cell renal carcinoma (CCRCC), by far the most common cancer subtype, is an aggressive tumor variant, serving in recent years as a prolific test bench research [...]

Language: Английский

Citations

1
CAR T cells in solid tumors and metastasis: paving the way forward DOI
Camilla Sirini,

Laura Rossi,

Marta Angiola Moresco

et al.

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(4), P. 1279 - 1296

Published: Sept. 24, 2024

Language: Английский

Citations

1