Vaishnavi Kardale, Bioinformatics Centre, Savitribai Phule Pune University
Head and neck cancer is the seventh most common type of cancer affecting people. It begins in the squamous cells of the head and neck region (mouth, throat, voice box). The squamous cells line the mucosal surface and hence this cancer is also known as head and neck squamous cell carcinoma (HNSCC). Some of the regions that make up the head and neck region like the brain, eye, esophagus, thyroid gland, and the skin of this region are not included in this type of cancer. The squamous cell carcinoma can metastasize to lymph nodes along with other regions in the body.
Treatment for HNSCC:
Radiotherapy is highly prescribed by physicians and plays an important role in the treatment of head and neck squamous cell carcinoma (HNSCC). It is included in the treatment plan of about one-half of head and neck cancer patients. Over time the tumour cells develop radioresistance. Radioresistance is a phenomenon where tumour cells become resistant to radiotherapy by adapting to radiotherapy-induced changes. It is crucial to overcome radioresistance in patients.
Mechanisms involved in clinical radioresistance:
According to researchers, putative mechanisms responsible for clinical radioresistance include:
● Hypoxic environment– The body part is deprived of oxygen
● EGFR-pathway alterations-The EGFR-pathway is responsible for cell growth and proliferation. Mutations in this pathway can cause cancer.
● Epithelial-Mesenchymal Transition (EMT)– This is a biological process where epithelial cells that are attached to basement membrane transition to mesenchymal cell phenotype. It enhances their migratory capacity, invasiveness, and resistance to apoptosis.
● Deregulation of p53– p53 controls cell division and death.
● Angiogenesis- This is the process of growth of blood vessels from existing vessels to the cancer cells.
A study recently published in BMC Cancer has developed a novel screening method for identification of radioresistance biomarkers in HNSCC.
What was the research about?
Prior investigation into biomarkers for HNSCC radioresistance has proven to be quite disappointing. In order to target the radioresistant cancer cell, it is essential to correctly identify clinically significant molecular events in the cancer cell lines, since in cancer research in vitro cell line investigation is first carried out, later followed by in-vivo studies. The diversity in the genome of different cancer cell lines complicates their selection. The selection of cell lines usually occurs by trial and error. This has created a high demand for a high-throughput screening method for cell line characteristics.
Findings from cell microarray techniques:
Johannes Routila et al. suggests the use of cell microarray for screening purposes. Cell microarray (CMA) is a powerful tool in the evaluation of cell lines. The absence of an extracellular matrix in the CMA facilitates the study of novel antibodies or other genomic methods. The cell lines can be studied in various cell line conditions The use of CMA as a fixed, paraffin-embedded biobank of a cell line is important, as it facilitates researchers to store the cell lines for later use after the relatively tedious original cell cultures. CMA is practical, saves time and is a cost-efficient way to determine the expression of a protein.
In their study, Johannes Routila et al. analyzed five putative biomarkers- p53, EGFR, Oct4, NDFIP1, and CIP2A – in head and neck squamous cell lines.
What did the study find?
The cells in CMA maintained their morphology and overall cellular architecture, leading to good staining results. This allowed for a reliable evaluation of immunohistochemical (IHC) stains. The use of CMA allowed for exclusively cellular material (cancer cell) to be analyzed using IHC and getting rid of the unspecific source of unwanted IHC signaling positivity. Manipulation and modification of a cell line are also possible with CMA allowing molecular profiling of cell lines by inhibiting or enhancing the expression of certain genes.
This can be used for drug development and drug discovery as now it is possible to expose the cell to drugs while culturing. According to the researchers, the downsides of CMA are that it fails to take into account patient- related factors like an immunological response, which may have an impact on the success of radiotherapy in HNSCC patients.
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Reference:
- Routila, J., Suvila, K., Grénman, R., Leivo, I., Westermarck, J., & Ventelä, S. (2021). Cancer cell line microarray as a novel screening method for identification of radioresistance biomarkers in head and neck squamous cell carcinoma. BMC Cancer, 21(1) 868. https://doi.org/10.1186/s12885-021-08618-6
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Author info:
Vaishnavi Kardale is a master’s student at the Bioinformatics Centre, Savitribai Phule University. She is interested in protein folding mechanisms and wants to study them further.
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