Related Experiment Video
Updated: Aug 13, 2026
Adaptation of Semiautomated Circulating Tumor Cell (CTC) Assays for Clinical and Preclinical Research Applications
Published on: February 28, 2014
[Report of the National Oncology Research and Developement Consortium, 2003]
1Nemzeti Onkológiai Kutatás-fejlesztési Konzorcium, Budapest, Hungary. jtimar@oncol.hu
Abstract:
Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type. Bone-metastatic tumors have been characterized by decreased NM23 and increased c-met and p53 expressions. C-erbB2 genotype of the primary tumor was not maintained frequently in bone metastases. Application of DNA-microarray and quantitative PCR technologies improved the prediction of therapeutic sensitivity of breast cancers. Colorectal cancer studies revealed regional inhomogenities (clusters) in various geographical regions of Hungary, which were distinct in the case of colonic and rectal cancers. To increase the sensitivity of fecal blood test of colorectal cancer screening, a new double-antibody test was developed and tested in a large cohort of patients. Genetic analysis revealed that hypermethylation is a significant factor in microsatellite instability which, and plays a role in silencing of APC and E-cadherin genes as well. The Hungarian pattern of TS polymorphism was also determined and was correlated not only with the efficacy of 5-FU treatment but with the progression of the disease as well. Population-based studies have been carried out in head and neck cancer patients (HNC) and smokers as well to reveal the genetic background of increasing tumor incidence. These studies revealed polymorphism in XRCC1/3 methylation enzyme gene which has preventive role. Other studies found frequent local immunosuppression in HNC patients. Studies indicated that the success of irradiation in this cancer type is dependent on the anti-vascular effects. Pediatric cancer studies determined the parameters of neuroblastoma screening based on VMA measurements. New splice variants of the WT1 gene involved in the monitoring of MRD of ALL patients was also described this year. We also obtained positive experimental data for the retinoic acid therapy of ALL. Melanoma studies extensively used DNA-microarray technology which identified 4 melanoma-specific and 2 melanoma progression-specific genes. In experimental human melanoma xenograft models we have identified 3 anti-metastatic agents: low molecular weight heparin, 2-methoxyestradiol and erythropoietin-alpha, where the later was characterized by specific effects on tumor vasculature.
Insights
This research explored five cancer types, identifying unique genetic markers and therapeutic sensitivities for breast, colorectal, head and neck, pediatric cancers, and melanoma. Findings advance cancer diagnostics and treatment strategies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Consortial projects investigated five major cancer types: breast, colorectal, head and neck, pediatric cancers, and malignant melanoma.
- Research focused on understanding the genetic underpinnings, diagnostic markers, and therapeutic sensitivities across these diverse malignancies.
Purpose of the Study:
- To elucidate unique splicing mechanisms in breast cancer involving BRCA1.
- To investigate the role of DNA-repair genes in sporadic breast cancers based on histological type.
- To characterize bone-metastatic tumors and identify novel therapeutic targets and predictive markers.
Main Methods:
- DNA-microarray and quantitative PCR for therapeutic sensitivity prediction in breast cancer.
- Development of a sensitive double-antibody fecal blood test for colorectal cancer screening.
- Genetic analysis including hypermethylation studies and TS polymorphism determination.
- Population-based studies on head and neck cancer (HNC) patients and smokers.
- VMA measurements for neuroblastoma screening and WT1 gene splice variant analysis for ALL.
- DNA-microarray technology for melanoma gene identification and xenograft models for anti-metastatic agent screening.
Main Results:
- Unique splicing mechanisms in breast cancer (BRCA1) and histological type-dependent DNA-repair gene involvement identified.
- Bone metastases characterized by altered gene expression (NM23, c-met, p53) and inconsistent C-erbB2 genotype.
- Regional variations in colorectal cancer and improved screening sensitivity via a new fecal blood test.
- Hypermethylation's role in microsatellite instability and gene silencing (APC, E-cadherin) confirmed; TS polymorphism correlated with 5-FU efficacy.
- Preventive role of XRCC1/3 polymorphism in HNC and association of irradiation success with anti-vascular effects.
- Parameters for neuroblastoma screening established; new WT1 splice variants for ALL monitoring and positive results for retinoic acid therapy.
- Identification of melanoma-specific/progression genes and three anti-metastatic agents (heparin, 2-methoxyestradiol, erythropoietin-alpha) in xenograft models.
Conclusions:
- The study identified key genetic and molecular alterations across five cancer types, improving understanding of disease mechanisms and progression.
- Novel diagnostic markers, screening tools, and potential therapeutic strategies were developed for breast, colorectal, pediatric cancers, and melanoma.
- Findings highlight the importance of histological type, genetic polymorphisms, and tumor microenvironment in cancer development and treatment response.
Related Concept Videos
02:59Cancer Prevention
Some...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:56Treatment Resistant Cancers
02:59Cancer Prevention
Some...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:56Treatment Resistent Cancers