Clinical application of liquid biopsy in colorectal cancer: detection, prediction, and treatment monitoring

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 16, 2024

Colorectal cancer (CRC) is one of the most prevalent malignancies affecting gastrointestinal tract and ranked third among cancers with highest incidence second-highest mortality rate worldwide. CRC exhibits a slow progression providing wide treatment window. The currently employed screening methods have shown great potential to prevent reduce CRC-related morbidity mortality. diagnosis achieved by colonoscopy tissue biopsy, studies showing that liquid biopsy more effective in detecting diagnosing early patients. Increasing number tumor components shed into circulating blood can be detected form, applied clinical management CRC. Analysis cells (CTCs), DNA (ctDNA), or tumor-associated platelets (TEPs) used for CRC, aid staging, response monitoring, prediction recurrence metastasis minimally invasive manner. This chapter provides an updated review CTCs, ctDNA, TEPs as novel biomarkers highlighting their strengths limitations.

Language: Английский

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WEE1 Inhibition by AZD1775 Augments Colorectal Cancer Cells Susceptibility to VE-822-induced DNA Damage and Apoptosis

Drug Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract WEE1 is a key tyrosine kinase involved in the cell cycle regulation with potent anticancer effects various cancer types including colorectal cancer. Recent studies have focused on potential of combinational inhibition Ataxia Telangiectasia and Rad-3-related protein (ATR) increasing apoptosis cells. Therefore, this study investigates inhibiting WEE1, by employing AZD1775, cellsʼ susceptibility to VE-822-induced DNA damage apoptosis. SW-480 HT-29 cells were treated AZD1775 VE-822, alone combination. MTT assay was used assess proliferation viability. The mRNA levels ATR, checkpoint 1 (CHK1), ribonucleotide reductase (RR) catalytic subunit M1 (RRM1) RRM2 measured qRT-PCR. Cellular γ-(H2A histone family member X) H2AX Western blot. Analyses conducted using ELISA 8-Oxo-2ʼ-deoxyguanosine (8-oxo-dG) levels. Lactate dehydrogenase (LDH) death assays low rate when VE-822 AZD1775. IC50 value for 1.3 μM 1.6 SW480 HT-29, respectively. Also, 140 nM 185 nM. expression CHK1, RRM1, significantly downregulated both lines combination (P<0.05). markers, γ-H2AX 8-oxo-dG upregulated these Simultaneous treatment AZD177 increased capacity lines. via potentiated ATR inhibitor, combating targeting damage.

Language: Английский

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MiR-3664-3p through suppressing ABCG2, CYP3A4, MCL1, and MLH1 increases the sensitivity of colorectal cancer cells to irinotecan.

Heliyon, Journal Year: 2025, Volume and Issue: unknown, P. e41933 - e41933

Published: Jan. 1, 2025

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy worldwide. Currently, irinotecan (CPT-11) used alone or in combination with other drugs to treat patients advanced CRC. However, 5-year survival rate for metastatic CRC remains below 10 %, largely due chemotherapy resistance. Several genes, including ABCG2, CYP3A4, MCL1, and MLH1 contribute This study aimed identify microRNAs that simultaneously regulate expression of these genes irinotecan-resistant cell lines their effect on resistant colorectal cells. Irinotecan-resistant were developed by intermittently exposing HCT116 SW480 gradually increasing doses over four generations. These designated HCT116-R1, HCT116-R2, HCT116-R3, HCT116-R4 SW480-R1, SW480-R2, SW480-R3, SW480-R4. The induction resistance was confirmed using MTT assays, calculating IC50 values each generation comparing them parental levels along miR-3664-3p, initially measured all quantitative real-time PCR. Following transfection HCT116-R3 SW480-R3 cells pre-miR-3664-3p, MLH1, miR-3664-3p re-evaluated In derived from SW480, increased MCL1 observed. a reduction CYP3A4 noted final both lines. Additionally, while HCT116-derived lines, no significant increase observed SW480-derived A consistent decrease found across When we transfected there an gene expression. led sensitivity irinotecan. It can be concluded considered regulator modulating genes.

Language: Английский

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Unmasking the Deceptive Nature of Cancer Stem Cells: The Role of CD133 in Revealing Their Secrets

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10910 - 10910

Published: June 30, 2023

Cancer remains a leading cause of death globally, and its complexity poses significant challenge to effective treatment. stem cells their markers have become key players in tumor growth progression. CD133, marker various cancer types, is an active research area as potential therapeutic target. This article explores the role CD133 treatment, beginning with overview statistics explanation markers. The rise discussed, including structure, functions, occurrence different types. Furthermore, covers target, focusing on gene therapy, immunotherapy, approaches affect expression. Nanoparticles such gold nanoparticles nanoliposomes are also discussed context CD133-targeted therapy. In conclusion, promising target for As this progresses, it hoped that therapies will offer new treatment options patients future.

Language: Английский

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Natural Products Treat Colorectal Cancer by Regulating miRNA

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(8), P. 1122 - 1122

Published: Aug. 9, 2023

Diseases are evolving as living standards continue to improve. Cancer is the main cause of death and a major public health problem that seriously threatens human life. Colorectal cancer one top ten most common malignant tumors in China, ranking second after gastric among gastrointestinal tumors, its incidence rate increasing dramatically each year due changes dietary habits lifestyle world’s population. Although conventional therapies, such surgery, chemotherapy, radiotherapy, have profoundly impacted treatment colorectal (CRC), drug resistance toxicity remain substantial challenges. Natural products, therapeutic agents, considered safest alternative for treating CRC. In addition, there evidence natural products can induce apoptosis, inhibit cell cycle arrest, reduce invasion migration colon cells by targeting regulating expression function miRNAs. Here, we summarize recent research findings on miRNA-regulation-based antitumor mechanisms various active ingredients highlighting how target miRNA regulation prevention treatment. The application delivery systems predictive disease biomarkers also discussed. Such approaches will contribute discovery new regulatory associated with pathways provide theoretical basis developing novel drugs compounds identifying targets.

Language: Английский

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Ataxia telangiectasia and Rad3-related (ATR) inhibition by VE-822 potently reversed 5-flourouracil resistance in colorectal cancer cells through targeting DNA damage response

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: March 29, 2024

Language: Английский

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Differential expression of angiogenesis-related genes ‘VEGF’ and ‘angiopoietin-1’ in metastatic and EMAST-positive colorectal cancer patients

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 8, 2024

Abnormal angiogenesis leads to tumor progression and metastasis in colorectal cancer (CRC). This study aimed elucidate the association between angiogenesis-related genes, including VEGF-A, ANGPT-1, ANGPT-2 with both metastatic microsatellite alterations at selected tetranucleotide repeats (EMAST) subtypes of CRC. We conducted a thorough assessment ANGPT-2, VEGF-A gene expression utilizing publicly available RNA sequencing microarray datasets. Then, experimental validation was performed 122 CRC patients, considering their disease EMAST

Language: Английский

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Insights on the Role of Polyphenols in Combating Cancer Drug Resistance

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1709 - 1709

Published: June 14, 2023

Chemotherapy resistance is still a serious problem in the treatment of most cancers. Many cellular and molecular mechanisms contribute to both inherent acquired drug resistance. They include use unaffected growth-signaling pathways, changes tumor microenvironment, active transport medicines out cell. The antioxidant capacity polyphenols their potential inhibit activation procarcinogens, cancer cell proliferation, metastasis, angiogenesis, as well promote inhibition or downregulation efflux transporters, have been linked reduced risk epidemiological studies. Polyphenols also ability alter immunological responses inflammatory cascades, trigger apoptosis cells. discovery relationship between abnormal growth signaling metabolic dysfunction cells highlights importance further investigating effects dietary polyphenols, including boost efficacy chemotherapy avoid multidrug (MDR). Here, it summarized what known regarding effectiveness natural polyphenolic compounds counteracting that might develop drugs result variety different mechanisms.

Language: Английский

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A perspective on emerging therapies in metastatic colorectal cancer: Focusing on molecular medicine and drug resistance

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(1)

Published: Jan. 1, 2024

Abstract The majority of cancer cases are colorectal cancer, which is also the second largest cause cancer‐related deaths worldwide. Metastasis leading death for patients with cancer. Metastatic incidence on rise due to a tiny percentage tumors developing resistant medicines despite advances in treatment tactics. Cutting‐edge targeted medications now go‐to option customized and all‐encompassing CRC care. Specifically, multitarget kinase inhibitors, antivascular endothelial growth factors, epidermal factor receptors widely used clinical practice CRC‐targeted treatments. Rare targets metastatic becoming more well‐known developments precision diagnostics extensive use second‐generation sequencing technology. These include KRAS mutation, BRAF V600E HER2 overexpression/amplification, MSI‐H/dMMR. Incorporating certain into trials has significantly increased patient survival rates, opening new avenues bringing fresh viewpoints treating focused therapies change how treated, giving hope better results. markers can transform individualize therapy regimens. They could open door precisely effective medicines, improving outcomes quality life. fast‐growing body knowledge regarding molecular biology latest gene directly responsible this advancement.

Language: Английский

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Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted Multiacting on Tumor Cell, Inactivating Cancer-Associated Fibroblast and Activating Immune Response

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(18), P. 16296 - 16310

Published: Sept. 5, 2024

To targeted overcome the multidrug resistance (MDR) and metastasis of liver tumors, we proposed to develop a palladium (Pd) agent based on specific residue human serum albumin (HSA) for multiacting tumor cell other components in microenvironment. this end, series Pd(II) 2-acetylpyridine thiosemicarbazone compounds were optimized obtain compound (5b) with significant cytotoxicity against HepG2/ADM cells. Subsequently, constructed HSA-5b complex delivery system revealed structural mechanism HSA delivering 5b. Importantly, 5b/HSA-5b effectively inhibited growth resistant enhanced targeting ability 5b reduced its side effects

Language: Английский

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