In this blog Dr. Antonio Giordano, Founder & Director of Sbarro Health Research Organization (SHRO) at Temple University talks about Retinoblastoma, why is it known as a childhood cancer risk, and how the scientific community is conducting research on this childhood cancer research field.
In Retinoblastoma, the cancer cells originate from the retina, or rather from the retinoblasts constituting the nervous tissue responsible for receiving light stimuli that are inside the eye. Although it can arise at all ages of the individual, from an epidemiological point of view, the vast majority of patients are children under the age of 5. This tumor presents at diagnosis with a rather broad spectrum of prognostic variability depending on the stage of progression of the neoplasm.
It is important to consider that scientific research on this childhood cancer in the last twenty years has recorded extremely important successes both by identifying the genetic alterations of this tumor and by greatly improving the therapeutic strategy. This has allowed not only survival but also an ever-increasing number of healing patients who, due to their tender age, have a very high potential life expectancy. Although unfortunately there are still very high disparities in both diagnosis and therapy between high-income countries and countries with low access to resources.
In Retinoblastoma, the cancer cells originate from the retina, or rather from the retinoblasts constituting the nervous tissue responsible for receiving light stimuli that are inside the eye. Although it can arise at all ages of the individual, from an epidemiological point of view, the vast majority of patients are children under the age of 5. This tumor presents at diagnosis with a rather broad spectrum of prognostic variability depending on the stage of progression of the neoplasm.
It is important to consider that scientific research on this childhood cancer in the last twenty years has recorded extremely important successes both by identifying the genetic alterations of this tumor and by greatly improving the therapeutic strategy. This has allowed not only survival but also an ever-increasing number of healing patients who, due to their tender age, have a very high potential life expectancy. Although unfortunately there are still very high disparities in both diagnosis and therapy between high-income countries and countries with low access to resources.
Retinoblastoma was the first human cancer in which an inheritance mechanism was demonstrated. The patient with hereditary neoplasia has a very high risk of developing the disease bilaterally (in both eyes), or in a minority of cases, even "trilaterally", when the neoplastic transformation affects the pineal gland at the base of the brain. In addition to being "hereditary", retinoblastoma can arise as a result of random events ("sporadic" retinoblastoma).
Precisely on the basis of these modalities of presentation of the tumor, Alfred Knudson 1971 developed the 'theory of two shots', according to which at least two mutational events are necessary for tumor development.
Molecular biology and biochemistry studies have identified a particular gene responsible for this tumor, the subject of these mutational events, which has been defined as RB (retinoblastoma). One-third of children with retinoblastoma have a germline (congenital) RB gene mutation. This means that all cells in the body have a defective RB gene. In most cases (75%), the mutation develops in the early stages of development, while for the remainder (25%), the genetic mutation is passed on from the parents. These children will tend to develop bilateral retinoblastoma and will be predisposed to developing tumors in other locations as well.
On the other hand, in two-thirds of cases (sporadic tumors), the mutation of the RB gene occurs during the first years of life in only one of the two eyes. Such children develop unilateral retinoblastoma and do not have the same increased susceptibility to cancer as children with the congenital form.
In addition to retinoblastoma, structural and/or functional alterations of the RB1 gene have also been found in other types of tumors. Research on this gene in oncology has multiplied once it has been shown that RB1 is a tumor suppressor gene and as such is able to counteract the potential onset of tumors in all tissues of the body. In particular, research has shown that RB1 is actually part of a larger family of tumor suppressor genes, which also includes RBL1 / p107 and RBL2 / p130.
The importance of these genes lies in the demonstration of the very important functions performed: not only of control of neoplastic growth but also of regulation of cellular processes of programmed death (apoptosis), differentiation, and senescence, all capable of counteracting the development and progression of the tumor.
Supporting scientific research in the study and treatment of Retinoblastoma, an intraocular malignant tumor that occurs mainly in the pediatric age is the best way to promote studies to find new preventive and therapeutic strategies in oncology.
In particular, the goal of many researchers today is to understand how it is possible to "turn off" the switch of the RB1 gene that gives rise to the development of cancer cells and their more or less rapid growth or how to "turn it on" to start the process of cell death.
From a clinical point of view, the specific knowledge that science has produced on the family of RB tumor suppressor genes has given rise to important studies on the correlation between genotype/phenotype and prognosis or on the correlation between genetic alteration and aggressiveness of the tumor and its prognosis. This could allow in the probably very near future a decisive "personalized therapy" of patients with retinoblastoma and perhaps also of patients with other tumors.
This article was published first in Italian on La Voce Di New York by Dr. Antonio Giordano, Founder & Director of Sbarro Health Research Organization at Temple University - College of Science and Technology, Philadelphia.
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