C400 Genetics : Therapy from Genomic and Geneticist Analyses

The diagnosis of the retinoblastoma is done via fundoscopy under general anaesthesia. The entire test procedure is performed via an ophthalmologist. This particular test helps in the elucidation of several parameters related to tumour like number, laterality, size, tumour seeding, sub retinal space and the specific anterior segment of the tumour. Further diagnostic imaging in this field assists in unfolding other associated brain abnormalities like intracranial tumour extension, midline intracranial primitiveneuroectodermal tumour (PNET) and other related brain malformations in retinoblastoma patients. The malformations are mostly severe in patients who are suffering from 13q deletion syndrome (de Graaf et al. 2012).

Conservative treatment strategies are found to be providing successful results if conducted during the early stages of the disease. The eye preservation therapy has been foundto provide positive results in recent years. This therapy is majorly based on the motive of tumour reduction and is given in collaboration with the chemotherapy, laser coagulation, radioactive plaque or cryotherapy. Recently, in order to treat the additional stages of the disease, selective ophthalmic artery infusion of a potential chemotherapeutic agent is made available. However, imaging is extremely important at local staging. A standardized MRI protocol is used to the imaging of the retinoblastoma patient before the onset of the treatment. The imaging technique helps in the process of lesion characterization and detection of the tumour extent (de Graaf et al. 2012).

Treatment management

At present, the cure rate for retinoblastoma is 85%, which is significant in the field of positive treatment but this cure of the disease usually occurs at cost of partial or complete loss of vision. Moreover, there is also an estimated mortality count of 50% in the developing countries. the patients who are suffering from RB lies at an increased risk of developing three of the major life-threatening conditions namely metastasis arising out of RB, brain tumour pinealoblastoma and primary level of cancer. At present the widely used treatment for RB, include cryotherapy, laser treatment and radiotherapy. Recently chemotherapy is systemic in nature and the main drugs used for this purpose include carboplatin, vincrisine and etoposide. These are all broad-spectrum antibiotics with dose limiting side effects like loss of hearing and other associated secondary cancers (Basavarajappa and Corson 2012).

Retinoblastoma is curable if there are no associated metastatic risk factors. The restoration of the visual function is dependent on the process of ocular preservation, anatomical relationships between the tumours of the macula and optic disk and the initial volume of the tumour. In the presence of the metastatic risk factors, adjuvant treatment therapy is prescribed in order to restrict a life-threatening relapse (de Graaf et al. 2012).

Retinoblastoma is regarded as the primary cause of the neoplasm in the pair of eyes during the early childhood. This debilitating disease in the industrialized sectors affects more than 95% of the children. Survival rate of the metastatic retinoblastoma was initially poor but with the advent of the high-dose chemotherapeutic agents followed by the autologous stem cell rescue (ASCR), the mortality rate of retinoblastoma decreased (Palma et al. 2012).

Retinoblastoma tumour has a heterogeneousmicro-environment that is made of high angiogenic activity along with low areas of oxygen tensed conditions. This oxygen-tensed condition becomes more pronounced during the advanced stage of the disease. The tumour cells, which grown within this hypoxic conditions are found resistant towards chemotherapeutic radiation. Treatment with glycolytic inhibitor 2-deoxy-2-fluro-D-glucose (2-FG) helps to reduce the load of tumour burden along with hypoxia in the retinal tumours. 2-FG is more potent glycolytic inhibitor under low oxygen concentration and thus helping to reduce the tumour in eyes arising out of retinoblastoma (Pina et al. 2012).

Future therapies

Despite significant advancement in the field of RB pathology and disease biology, there are till date no targeted chemotherapies available for the disease treatment. At present, efforts are being made to use KIF14, an oncogene for retinoblastoma as a novel target for therapeutics. Identification of the 1q31 region of the RB gene led to the discovery of KIF14. KIF14 is over-expressed at the mRNA level with excess genomic gain. Moreover, the over-expression of KIF14 has been confirmed via carrying a study in an independent RB cohort. These information are now being significantly utilized by Basavarajappa and Corson (2012)inorder to develop novel therapeutic approach for RB.

Conclusion:

Thus from the above discussion it can be concluded that retinoblastoma is an intraocular cancer that is caused by the loss of either single or both the copies of Rb gene. The disease primarily affects children who are below 5 years of age. Rb gene is normal involved in the cell cycle progression and faults in the phosphorylation leads to the tumour development. At present treatment of retinoblastoma leads to either enucleation or chemotherapy or cryotherapy. However, latest research is being carried out to elucidate novel therapeutic approach.

References:

Alberts, B., Bray, D., Hopkin, K., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P., 2013. Essential cell biology. Garland Science.

Basavarajappa, H.D. and Corson, T.W., 2012. KIF14 as an oncogene in retinoblastoma: a target for novel therapeutics?. Future medicinal chemistry, 4(17), pp.2149-2152.

Bertoli, C., Skotheim, J.M. and De Bruin, R.A., 2013. Control of cell cycle transcription during G1 and S phases. Nature reviews Molecular cell biology, 14(8), pp.518-528.

Chinnam, M. and Goodrich, D.W., 2011. RB1, development, and cancer. Current topics in developmental biology, 94, p.129.

Cooper, G.M. and Hausman, R.E., 2010. The cell (Vol. 85).Sunderland: Sinauer Associates.

deGraaf, P., Göricke, S., Rodjan, F., Galluzzi, P., Maeder, P., Castelijns, J.A., Brisse, H.J. and European Retinoblastoma Imaging Collaboration, 2012. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatric radiology, 42(1), pp.2-14.

Grossniklaus, H.E., 2014. Retinoblastoma.Fifty years of progress.The LXXI Edward Jackson memorial lecture. American journal of ophthalmology, 158(5), pp.875-891.

Palma, J., Sasso, D.F., Dufort, G., Koop, K., Sampor, C., Diez, B., Richard, L., Castillo, L. and Chantada, G.L., 2012. Successful treatment of metastatic retinoblastoma with high-dose chemotherapy and autologous stem cell rescue in South America. Bone marrow transplantation, 47(4), pp.522-527.

Pina, Y., Decatur, C., Murray, T.G., Houston, S.K., Lopez-Cavalcante, M., Hernandez, E., Celdran, M., Shah, N., Feuer, W. and Lampidis, T., 2012.Retinoblastoma treatment: utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-D-glucose (2-FG), to target the chemoresistant hypoxic regions in LHBETATAG retinal tumours. Investigative ophthalmology & visual science, 53(2), pp.996-1002.

Zhang, J., Benavente, C.A., McEvoy, J., Flores-Otero, J., Ding, L., Chen, X., Ulyanov, A., Wu, G., Wilson, M., Wang, J. and Brennan, R., 2012.A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature, 481(7381), pp.329-334.