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Glycolysis Role in Rhabdomyosarcomas

published: 21 Nov 2011 (2:57)
A study conducted by the IDIBELL researchers claims that inhibiting glucose metabolism with a substance called 2-Deoxyglucose (2-DG) may help in curing a rare cancer of skeletal tissue origin. This study about killing tumour cells in Rhabdomyosarcoma has been published in the Cancer Research journal. 2-DG has an action similar to that of the molecule used in positive emission tomography (PET) which scans tumours and offers a diagnosis according to the rate of consumption of glucose by the tumour cells. This might as well be used as a treatment protocol for Rhabdomyosarcoma, a rare cancer of skeletal tissue origin prevalent in children.

Rhabdomyosarcoma is rarely seen in adults but it happens to be one of the most common soft tissue tumours in children and adolescents. 4-5% of paediatric tumours are rhabdomyosarcomas. Among the two variants, embryonic and alveolar, the latter is more aggressive and has a poorer prognosis. Conventional treatment modalities like chemotherapy are ineffective against this deadly tumour. The most widely accepted treatment plan is surgical excision of the tumour. Even with surgery, the survival rate five years after the diagnosis is only 70%. This kind of prognosis has necessitated the quest for more efficient newer therapies.

The key to killing the tumour cell lies in studying its origin. Tumour metabolism has been studied to analyse the occurrence and initiation of the cancer for many years now. Glycolysis (breaking down of glucose into smaller molecules to release energy in the form of ATP) is a pathway of key role in some tumour masses. Rate of glycolysis is substantially increased in some of the tumour cells. A tumour cell that acquires its energy from glycolysis would be killed if glycolysis is inhibited with the help of molecules like 2-deoxyglucose.

A test-tube study conducted by the heads of the group of Cell Death Regulation and the group of Sarcomas revealed that when glycolysis was inhibited in the tumour cells in vitro, their metabolism was affected and the cells eventually died. Cristina Muñoz-Pinedo, head of the group of Cell Death Regulation heralded that 2-DG retards the growth of the tumour and consequently causes their death. A few of the tumour cells undergo differentiation and present themselves as healthy muscle cells.

Action of 2-DG is quite similar to the radioactive substances used in PET scans, only safer. On the basis of many experiments being conducted around the world, it has been inferred that 2-deoxyglucose has a low toxicity rate and this may be used as a potential treatment for curing alveolar variants of rhabdomyosarcoma. According to Cristina Muñoz-Pinedo, this study has opened the doors for customized treatment modalities which would work on the grounds of the origin and growth of tumour cells.

S. Ramirez-Peinado, F. Alcazar-Limones, L. Lagares-Tena, N. El Mjiyad, A. Caro-Maldonado, O. M. Tirado, C. Munoz-Pinedo. 2-deoxyglucose induces Noxa-dependent apoptosis in alveolar rhabdomyosarcoma. Cancer Research, 2011; DOI: 10.1158/0008-5472.CAN-11-0759

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