Difference between revisions of "Team:CLSB-UK"

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{{CLSB-UK Image Container Left Start|image=<svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 140 182.8"><path fill="#c62828" d="M63.5 52.7H101L31 173.3c-4.8 5.6-10 10.6-21 6.5-7-4.7-11.3-11-6-23z"/><path fill="none" stroke="#000" stroke-width="2.9" d="M123.8 21.8l-4-2.3-87.8 152c-6 10.5-16 11.8-23 8-6.8-4-10.6-13.4-4.6-24l87.8-152-4-2.2"/></svg>|title=Biomarkers in the blood}}
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Abnormal levels of miRNAs mir-15b-5p and mir-27b-3p in blood serum are indicative of NSCLC[2]. We have designed two sequence-specific sensors that utilise synthetic riboregulators called toehold switches. These toehold switches detect mir-15b-5p and mir-27b-3p and produce fluorescent reporter proteins in their presence. We designed our sensors to work in a cell-free system, allowing them to be used safely and in a low-tech environment.
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Abnormal levels of miRNAs mir-15b-5p and mir-27b-3p in blood serum are indicative of NSCLC<ref name="Hennessey">Hennessey, P. T., Sanford, T., Choudhary, A., Mydlarz, W. W., Brown, D., Adai, A. T., & Califano, J. A. (2012). Serum microRNA biomarkers for detection of non-small cell lung cancer. PloS one, 7(2), e32307.</ref>. We have designed two sequence-specific sensors that utilise synthetic riboregulators called toehold switches. These toehold switches detect mir-15b-5p and mir-27b-3p and produce fluorescent reporter proteins in their presence. We designed our sensors to work in a cell-free system, allowing them to be used safely and in a low-tech environment.
 
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Lung cancer is the most common cause of cancer-related mortality, with 1.6 million deaths in 2012. That’s 20% of all reported deaths due to cancer. Non-small cell lung cancer (NSCLC) makes up ~80% of all incidences of lung cancer. 58% of all cases in 2012 were reported in less developed countries.[4] NSCLC is characteristically aggressive and pathologically diverse.[5] Common subtypes include pulmonary adenocarcinoma (~50%) and squamous cell carcinoma (~40%).<br><br>Treatment still centres around cytotoxic chemotherapy, although new treatments show promise including immunotherapies.[6][3] NSCLC’s high mortality rate is, in large part, down to the late stage at which the disease is normally diagnosed.[7] This often renders surgery, which can curative in early stages, pointless as the tumour has metastasised.[8][9]<br><br>About 90% of lung cancers are caused by smoking and as smoking rates have declined, there has been a corresponding reduction in incidence of lung cancers.[10] However, nearly 30% of the global population are still estimated to smoke.[11]
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Lung cancer is the most common cause of cancer-related mortality, with 1.6million deaths in 2012. That’s 20% of all reported deaths due to cancer. Non-small cell lung cancer (NSCLC) makes up ~80% of all incidences of lung cancer.<ref name="chan">Chan, B. A., & Hughes, B. G. (2015). Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Translational lung cancer research, 4(1), 36.</ref> 58% of all cases in 2012 were reported in less developed countries.<ref>Ferlay, J., Soerjomataram, I., & Ervik, M. (2012). GLOBOCAN, cancer incidence and mortality worldwide: IARC cancer base no. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013.</ref>
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NSCLC is characteristically aggressive and pathologically diverse.<ref>Board, P. A. T. E. (2017). Non-Small Cell Lung Cancer Treatment (PDQ®).</ref> Common subtypes include pulmonary adenocarcinoma (~50%) and squamous cell carcinoma (~40%). The classification of the original tumour will impact prognosis and treatment. Treatment still centres around cytotoxic chemotherapy, although new treatments show promise including immunotherapies.<ref>Chen, Z., Fillmore, C. M., Hammerman, P. S., Kim, C. F., & Wong, K. K. (2014). Non-small-cell lung cancers: a heterogeneous set of diseases. Nature reviews. Cancer, 14(8), 535.</ref><ref name="chan" />
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NSCLC’s high mortality rate is, in large part, down to the late stage at which the disease is normally diagnosed.<ref name="dajac">Dajac, J., Kamdar, J., Moats, A., & Nguyen, B. (2016). To Screen or not to Screen: Low Dose Computed Tomography in Comparison to Chest Radiography or Usual Care in Reducing Morbidity and Mortality from Lung Cancer. Cureus, 8(4).</ref> This often renders surgery, which can curative in early stages, pointless as the tumour has metastasised.<ref> Uramoto, H., & Tanaka, F. (2014). Recurrence after surgery in patients with NSCLC. Translational lung cancer research, 3(4), 242.</ref><ref>Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008, May). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. In Mayo Clinic Proceedings(Vol. 83, No. 5, pp. 584-594). Elsevier.</ref>
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About 90% of lung cancers are caused by smoking and as smoking rates have declined, there has been a corresponding reduction in incidence of lung cancers.<ref> (n.d.). Lung cancer: diagnosis and management - NICE. Retrieved October 7, 2017, from https://www.nice.org.uk/guidance/cg121/chapter/introduction</ref> However, nearly 30% of the global population are still estimated to smoke.<ref name="gopal">Gopal, M., Abdullah, S. E., Grady, J. J., & Goodwin, J. S. (2010). Screening for lung cancer with low-dose computed tomography: a systematic review and meta-analysis of the baseline findings of randomized controlled trials. Journal of thoracic oncology, 5(8), 1233-1239.</ref>
 
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Revision as of 23:41, 14 October 2017

Project BATMAN

a new way to detect cancer using toehold switches

Late presentation and non-specific symptoms are the main
reasons 1.6 million people worldwide die from lung cancer every year

Dr Sujal Desai, Consultant Chest Radiologist

We have developed a new way to detect cancer at an early stage by measuring micro-RNAs (miRNAs), biomarkers found in blood. We use toehold switches to regulate expression of GFP in response to specific miRNAs. This method could be applied to a myriad of diseases, but we have chosen to use non-small cell lung cancer (NSCLC) as a proof of concept. We hope our work in NSCLC detection demonstrates the potential that toehold switches have to offer as a cheap and effective diagnostic tool.

Late presentation of symptoms is the main reason
why 40,000 people are dying every year from lung cancer

Dr Sujal Desai, Respiratory Consultant

We developed a new way to detect cancer at an early stage by measuring micro-RNAs (miRNA), biomarkers found in blood. We used toehold switches to regulate expression of GFP in response to specific miRNAs. This method could be applied to a myriad of diseases, but we have chosen to use non-small cell lung cancer as a proof of concept.

Biomarkers in the blood

Abnormal levels of miRNAs mir-15b-5p and mir-27b-3p in blood serum are indicative of NSCLC[1]. We have designed two sequence-specific sensors that utilise synthetic riboregulators called toehold switches. These toehold switches detect mir-15b-5p and mir-27b-3p and produce fluorescent reporter proteins in their presence. We designed our sensors to work in a cell-free system, allowing them to be used safely and in a low-tech environment.

Non-small cell lung cancer

Lung cancer is the most common cause of cancer-related mortality, with 1.6million deaths in 2012. That’s 20% of all reported deaths due to cancer. Non-small cell lung cancer (NSCLC) makes up ~80% of all incidences of lung cancer.[2] 58% of all cases in 2012 were reported in less developed countries.[3]

NSCLC is characteristically aggressive and pathologically diverse.[4] Common subtypes include pulmonary adenocarcinoma (~50%) and squamous cell carcinoma (~40%). The classification of the original tumour will impact prognosis and treatment. Treatment still centres around cytotoxic chemotherapy, although new treatments show promise including immunotherapies.[5][2]

NSCLC’s high mortality rate is, in large part, down to the late stage at which the disease is normally diagnosed.[6] This often renders surgery, which can curative in early stages, pointless as the tumour has metastasised.[7][8]

About 90% of lung cancers are caused by smoking and as smoking rates have declined, there has been a corresponding reduction in incidence of lung cancers.[9] However, nearly 30% of the global population are still estimated to smoke.[10]

  1. ↑ Hennessey, P. T., Sanford, T., Choudhary, A., Mydlarz, W. W., Brown, D., Adai, A. T., & Califano, J. A. (2012). Serum microRNA biomarkers for detection of non-small cell lung cancer. PloS one, 7(2), e32307.
  2. ↑ 2.0 2.1 Chan, B. A., & Hughes, B. G. (2015). Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Translational lung cancer research, 4(1), 36.
  3. ↑ Ferlay, J., Soerjomataram, I., & Ervik, M. (2012). GLOBOCAN, cancer incidence and mortality worldwide: IARC cancer base no. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013.
  4. ↑ Board, P. A. T. E. (2017). Non-Small Cell Lung Cancer Treatment (PDQ®).
  5. ↑ Chen, Z., Fillmore, C. M., Hammerman, P. S., Kim, C. F., & Wong, K. K. (2014). Non-small-cell lung cancers: a heterogeneous set of diseases. Nature reviews. Cancer, 14(8), 535.
  6. ↑ Dajac, J., Kamdar, J., Moats, A., & Nguyen, B. (2016). To Screen or not to Screen: Low Dose Computed Tomography in Comparison to Chest Radiography or Usual Care in Reducing Morbidity and Mortality from Lung Cancer. Cureus, 8(4).
  7. ↑ Uramoto, H., & Tanaka, F. (2014). Recurrence after surgery in patients with NSCLC. Translational lung cancer research, 3(4), 242.
  8. ↑ Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008, May). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. In Mayo Clinic Proceedings(Vol. 83, No. 5, pp. 584-594). Elsevier.
  9. ↑ (n.d.). Lung cancer: diagnosis and management - NICE. Retrieved October 7, 2017, from https://www.nice.org.uk/guidance/cg121/chapter/introduction
  10. ↑ Gopal, M., Abdullah, S. E., Grady, J. J., & Goodwin, J. S. (2010). Screening for lung cancer with low-dose computed tomography: a systematic review and meta-analysis of the baseline findings of randomized controlled trials. Journal of thoracic oncology, 5(8), 1233-1239.