Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer
| Autor: | Elisa Varriale, Linda Plappert, Enrico Cortesi, Paola Gazzaniga, Chiara Nicolazzo, Elena De Falco, Angela Gradilone, Cristina Raimondi, Giuseppe Giannini, Siegfried Hauch, Isotta Chimenti |
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| Rok vydání: | 2014 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Colorectal cancer colorectal cancer circulating tumor cells Biology medicine.disease_cause Proto-Oncogene Proteins p21(ras) Prostate cancer Circulating tumor cell Internal medicine Proto-Oncogene Proteins tumor heterogeneity medicine kras biomarker Humans Liquid biopsy Neoplasm Metastasis KRAS Gene Amplification Aged Pharmacology Aged 80 and over Gene Amplification Middle Aged medicine.disease Neoplastic Cells Circulating Primary tumor ErbB Receptors Mutation Cancer research ras Proteins Clinical Study Molecular Medicine Biomarker (medicine) Female KRAS Colorectal Neoplasms Signal Transduction |
| Zdroj: | Cancer biologytherapy. 15(5) |
| ISSN: | 1555-8576 |
| Popis: | The hypothesis of the “liquid biopsy” using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients using CellSearch, the only FDA-cleared test for CTCs assessment, demonstrated a much lower yield of CTCs in this tumor type compared with breast and prostate cancer, both at baseline and during the course of treatment. Thus, although attractive, the possibility to use CTCs as therapy-related biomarker for colorectal cancer patients is still limited by a number of technical issues mainly due to the low sensitivity of the CellSearch method. In the present study we found a significant discordance between CellSearch and AdnaTest in the detection of CTCs from mCRC patients. We then investigated KRAS pathway activating mutations in CTCs and determined the degree of heterogeneity for KRAS oncogenic mutations between CTCs and tumor tissues. Whether KRAS gene amplification may represent an alternative pathway responsible for KRAS activation was further explored. KRAS gene amplification emerged as a functionally equivalent and mutually exclusive mechanism of KRAS pathway activation in CTCs, possibly related to transcriptional activation. The serial assessment of CTCs may represent an early biomarker of treatment response, able to overcome the intrinsic limit of current molecular biomarkers represented by intratumor heterogeneity. |
| Databáze: | OpenAIRE |
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