Dr Helen Roberts (née Owen) was the winner of the Strictly Research Award during our 2017 Bone Cancer Conference
Background of the research:
Resistance to chemotherapy (chemoresistance) is a large obstacle in the effective treatment of osteosarcoma. Although chemotherapy has advanced significantly, many improvements are still required for osteosarcoma patients’ survival to improve and many researchers believe this is only possible if we can overcome chemotherapy resistance.
A process known as “autophagy” (self-degradation) can act as a protective cell survival mechanism that helps cancer cells thrive under chemotherapeutic stress.
Autophagy promotes cell survival by recycling damaged cellular components and providing the cell with energy; some studies have shown that cancer cells use this mechanism to survive during drug treatment. It seems that in osteosarcoma, sometimes, autophagy can promote cell survival, and in other circumstances, it contributes to cell death, depending on the type of tumour.
Results of the study:
The first objective of the research project led by Dr Helen Roberts (née Owen) was to investigate the link between autophagy and osteosarcoma, and to identify the role that autophagy plays in controlling drug resistance in different grades of osteosarcoma.
The research group found that a key marker of autophagy (a protein called LC3) was present at higher levels in most advanced tumour tissues, compared to less advanced and to normal bone. They also found that high levels of LC3 correlated with poor disease outcome and a reduced chance of surviving free of tumour metastasis.
Osteosarcoma cells of varying grades were treated with drugs which are commonly used to treat osteosarcoma (doxorubicin and cisplatin), and the autophagy pathway was then examined. Levels of LC3 were increased in high-grade osteosarcoma cells treated with chemotherapy drugs compared to low grade cells. When the autophagy pathway was blocked by stopping LC3 synthesis, the high-grade cells became more sensitive to chemotherapy.
These results suggest that autophagy plays a key role in causing drug resistance in metastatic osteosarcoma.
The availability of a biological marker (‘biomarker’) that could be measured in a blood sample to predict how a disease will react to different drugs is one of the ‘holy grails’ in cancer research.
Over the past 10 years microRNAs have been shown to possess many of the desirable characteristics for such a biomarker. MicroRNAs (miRs) are very stable molecules that have the potential to regulate various critical biological processes, including the multiplication and spread of tumour cells. Several miRs have been shown to control osteosarcoma spread and drug resistance through the autophagy pathway. Therefore, the second aim of the project was to identify miRs that regulate autophagy in osteosarcoma following drug treatment, as a potential tool for predicting how patients will react to different therapeutic regimes.
2 miRs were identified that targeted 2 important regulators of the autophagy pathway in high grade osteosarcoma cells.
Further research is being carried out to determine if these miRs would be suitable biomarkers that could predict how a particular osteosarcoma tumour will respond to treatment.