Cetuximab enhances radiosensitivity of esophageal squamous cell carcinoma cells by G2/M cycle arrest and DNA repair delay through inhibiting p‐EGFR and p‐ERK DOI Creative Commons
Guifang Zhao, Liwen Feng, Ting Ye

et al.

Thoracic Cancer, Journal Year: 2023, Volume and Issue: 14(22), P. 2127 - 2138

Published: June 20, 2023

Abstract Background Although radiotherapy has improved local control in esophageal squamous cell carcinoma (ESCC), a considerable number of patients still experience relapse due to resistance. In this study, we aimed evaluate the effects cetuximab on radiosensitivity two ESCC lines (ECA109 and TE‐13) investigate their underlying mechanisms. Methods Cells were pretreated with or without before irradiation. The MTT assay clonogenic survival performed viability radiosensitivity. Flow cytometry was analyze cycle distribution apoptosis. γH2AX foci counted determine cellular DNA‐repairing capacity via immunofluorescence assay. phosphorylation key molecules involved epidermal growth factor receptor (EGFR) signaling pathway DNA double‐strand break (DSB) repair measured by western blot. Results Cetuximab alone not sufficient suppress viability, but significantly enhanced radiation‐induced inhibition ECA109 TE‐13. radiation sensitivity enhancement ratio (SER) 1.341 1.237 for TE‐13, respectively. cells treated arrested at G2/M phase response radiation. No significant increase apoptotic rate observed irradiated that cetuximab. average increased combination group (cetuximab radiation). suppressed EGFR downstream ERK, had no effect AKT. Conclusions These results indicate potential use as an effective radiosensitizer ESCC. promotes arrest reduces DSB repair, well inhibiting ERK pathways

Language: Английский

Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond DOI Creative Commons
Samar Al Bitar,

Marwan El‐Sabban,

Samer Doughan

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(9), P. 1395 - 1426

Published: March 7, 2023

Colorectal cancer (CRC) is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide. Despite advances in therapeutic regimens, number patients presenting with metastatic CRC (mCRC) increasing due to resistance therapy, conferred by small population cells, known as stem cells. Targeted therapies have been highly successful prolonging overall survival mCRC. Agents are being developed target key molecules involved drug-resistance metastasis CRC, these include vascular endothelial growth factor, epidermal factor receptor, human receptor-2, mitogen-activated extracellular signal-regulated kinase, addition immune checkpoints. Currently, there several ongoing clinical trials newly targeted agents, which shown considerable efficacy improved prognosis who do not benefit from conventional chemotherapy. In this review, we highlight recent developments use existing novel agents against drug-resistant Furthermore, discuss limitations challenges associated therapy strategies combat intrinsic acquired therapies, importance implementing better preclinical models application personalized based on predictive biomarkers for treatment selection.

Language: Английский

Citations

37
Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy DOI Creative Commons
Paulina Czajka‐Francuz,

Maria J. Prendes,

Arun K. Mankan

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 22, 2023

The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape have been identified. These include not only processes associated with tumor, or stromal cells, but also humoral, metabolic, genetic and epigenetic factors TME. identification has enabled development small molecules, nanomedicines, checkpoint inhibitors, adoptive cell that can reprogram TME shift host response towards promoting an antitumor effect. approaches translated into series breakthroughs in therapies, some which already implemented clinical practice. In present article authors provide overview most important immunosuppression implications for targeted against different cancers.

Language: Английский

Citations

25
Exploring the integration of nanotechnology in the development and application of biosensors for enhanced detection and monitoring of colorectal cancer DOI
Ashkan Hajjafari, Soheil Sadr, Abbas Rahdar

et al.

Inorganic Chemistry Communications, Journal Year: 2024, Volume and Issue: 164, P. 112409 - 112409

Published: April 12, 2024

Language: Английский

Citations

15
NK Cell-Based Immunotherapy in Colorectal Cancer DOI Creative Commons

Mariella Della Chiesa,

Chiara Setti,

Chiara Giordano

et al.

Vaccines, Journal Year: 2022, Volume and Issue: 10(7), P. 1033 - 1033

Published: June 28, 2022

Human Natural Killer (NK) cells are all round players in immunity thanks to their powerful and immediate response against transformed the ability modulate subsequent adaptive immune response. The potential of immunotherapies based on NK cell involvement has been initially revealed hematological setting but inspired design different tools also be applied solid tumors, including colorectal cancer (CRC). Indeed, despite prevention screening plans, surgery, chemotherapy strategies, CRC is one most widespread cancers with highest mortality rate. Therefore, further efficient complementary immune-based therapies urgent need. In this review, we gathered recent advances cell-based aimed at fighting CRC, particular, use monoclonal antibodies targeting tumor-associated antigens (TAAs), checkpoint blockade, adoptive therapy, modified chimeric antigen receptor (CAR-NK).

Language: Английский

Citations

26
Inhibition of Human Colorectal Cancer by a Natural Product 7-Acetylhorminone and Interactions with BSA/HSA: Multispectral Analysis and In Silico and In Vitro Studies DOI
Sourav Pakrashy, Souvik Chakraborty, Sounik Manna

et al.

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(5), P. 3414 - 3430

Published: April 30, 2024

We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed the set parameters pharmacokinetics (most important nonblood–brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) most other phytoconstituents failed to pass combined with docking EGFR protein highly upregulated in carcinoma cell. The structure was confirmed by single crystal X-ray diffraction studies 1H NMR, 13C COSY studies. To validate theoretical studies, first, vitro experiments were carried out human cell lines (HCT116) revealed potent cytotoxic efficacy verified preliminary investigation. Second, drugability interaction serum albumin proteins (HSA BSA) evaluated both theoretically experimentally via steady-state fluorescence spectroscopic circular dichroism, isothermal titration calorimetry, molecular docking. In summary, this study reveals applicability candidate or combinatorial cancer.

Language: Английский

Citations

5
Integrative multi-omics profiling of colorectal cancer from a Hispanic/Latino cohort of patients DOI Creative Commons
Brigette Waldrup, Francisco Carranza, Yuxin Jin

et al.

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

Published: Nov. 4, 2024

ABSTRACT Colorectal cancer contributes to cancer-related deaths and health disparities in the Hispanic Latino community. To probe both biological genetic bases of disparities, we characterized features colorectal terms somatic alterations similarity. Specifically, conducted a comprehensive genome-scale analysis 67 samples. We performed DNA exome sequencing for mutations, copy number alterations, also RNA differential gene expression, cellular pathways, fusions. analyzed all samples 22 important CRC 8 amplifications, 25 Then, compared our data from publicly available, Non-Hispanic White (NHW) cohorts. According analyses, twenty-four percent carcinomas were hypermutated when patients Peruvians-from-Lima-like (1KG-PEL-like) similarity population 1000 genome project. Moreover, most these cases occurred who less than fifty years old age at diagnosis. Excluding tumors, approximately 55% colon cancers 58% rectum exhibited two similar features: 1) patterns genomic alterations; 2) percentage 1KG-PEL-like. -- which had median 1KG-PEL-like proportion One notable example frequently observed mutation was SMAD4. Samples with SMAD4 are known support tumor growth progression, highest (63%). results risk association analyses significant NHW Of drug-targetable PIK3CA PI3K an average over 55%. relevant fusions, targetable genes included ALK, FGFR1, RAF1, PTPRK; PTPRK sample (95%). Using integrative analysis, detected recurrent WNT, TGFB, TP53, IGF2/PI3K, RTK/RAS pathways. Importantly, mostly young high These findings highlight potential tailoring precision medicine therapeutics underrepresented population. Our study advances molecular profiling Hispanics Latinos. In toto, appears be component understanding carcinogenesis has advance research. Significance provides profiles underserved community, probes impact similarity, sheds light on disparities. This comprehensive, (CRCs) taken patients. general, cohort presented (55%) (24% cases) predominantly individuals Most (<50) assessed cross-referenced For example, frequent mutations suppressor called SMAD4; 63% PTPRK. 95% proportion. thus Latinos; suggests can tailored community; demonstrates carcinogenesis.

Language: Английский

Citations

5
Colorectal Cancer Chemoprevention: A Dream Coming True? DOI Open Access
Martina Lepore Signorile, Valentina Grossi, Candida Fasano

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7597 - 7597

Published: April 20, 2023

Colorectal cancer (CRC) is one of the deadliest forms worldwide. CRC development occurs mainly through adenoma-carcinoma sequence, which can last decades, giving opportunity for primary prevention and early detection. involves different approaches, ranging from fecal occult blood testing colonoscopy screening to chemoprevention. In this review, we discuss main findings gathered in field chemoprevention, focusing on target populations various precancerous lesions that be used as efficacy evaluation endpoints The ideal chemopreventive agent should well tolerated easy administer, with low side effects. Moreover, it readily available at a cost. These properties are crucial because these compounds meant long time risk profiles. Several agents have been investigated so far, some currently clinical practice. However, further investigation needed devise comprehensive effective chemoprevention strategy CRC.

Language: Английский

Citations

13
Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview DOI Creative Commons
Jingjing Li,

Xuan-Fu Xu

International Journal of General Medicine, Journal Year: 2023, Volume and Issue: Volume 16, P. 1527 - 1540

Published: April 1, 2023

Colorectal cancer (CRC) is one of the most common diseases in world. Tumor immunotherapy an innovative treatment that acts by activating human body's autoimmune system. Immune checkpoint block has been shown to be effective DNA deficient mismatch repair/microsatellite instability-high CRC. However, therapeutic effect for proficient stability patients still requires further study and optimization. At present, main CRC strategy combine other methods, such as chemotherapy, targeted therapy, radiotherapy. Here, we review current status latest progress immune inhibitors same time, consider opportunities transforming cold hot, well perspectives on possible future therapies, which may great demand drug-resistant patients.

Language: Английский

Citations

11
Unveiling the genetic and epigenetic landscape of colorectal cancer: new insights into pathogenic pathways DOI
Humzah Postwala, Yesha Shah, Priyajeet S. Parekh

et al.

Medical Oncology, Journal Year: 2023, Volume and Issue: 40(11)

Published: Oct. 19, 2023

Language: Английский

Citations

10
The role of monoclonal antibodies in the treatment of pancreatic and colon cancers DOI
Soumya Dakshinamurthy

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 389 - 412

Published: Jan. 1, 2025

Language: Английский

Citations

0