Indian Scientists Discover New Protein To Treat Pediatric Cancer

Scientists unearthed the role of a protein that manages the function of a cancer-causing gene in development of RMS

Updated03 Feb 2019, 05:39 AM IST
Cancer
5 min read

About 40,000 children each year are struck by cancer in India. To ensure affected children can go back to their normal lives, scientists are peering deep inside molecules to help develop better treatment strategies for some of the rare and lethal pediatric tumours out there.

According to pediatric oncologist Girish Chinnaswamy, as across the world, in India too acute leukemias are the most common, followed by brain tumors and then other solid tumours. Some tumors like retinoblastoma are reported at a higher incidence in India compared to high income countries.

What is Rhabdomyosarcoma (RMS)?

Rhabdomyosarcoma (RMS) is a solid tumour, that accounts for about three percent of all childhood cancers.
Rhabdomyosarcoma (RMS) is a solid tumour, that accounts for about three percent of all childhood cancers.
(Photo: Wikipedia Commons)

Rhabdomyosarcoma (RMS) is a solid tumour, that accounts for about three percent of all childhood cancers. It is the most prevalent soft tissue cancer and it generally develops in the muscles around the bone that are responsible for movement, and slowly spreads to other parts of the body. It can affect the head, neck, bladder, arms, legs, or any body part.

Now a new study by Sam Mathew and his group at Regional Centre for Biotechnology has brought in fresh insights on potential therapeutic intervention for RMS, an aggressive and highly malignant cancer.

The group unearthed the role of a protein that manages the function of a cancer-causing gene in the development of RMS.
The group unearthed the role of a protein that manages the function of a cancer-causing gene in the development of RMS.
(Photo: iStockphoto)

The group unearthed the role of a protein that manages the function of a cancer-causing gene in the development of RMS. They hoped that a better understanding of the tumour machinery could lead to entirely new treatment approaches.

MET is a cancer-causing gene (oncogene) and it encodes a protein that helps control cell growth, survival and movement. The MET gene is mutated and its management and regulation is messed up in numerous types of cancers, such as in RMS.

In RMS, MET (protein) levels are known to be mis-regulated and our study was aimed at understanding the mechanism controlling MET mis-regulation in RMS.
Sam Mathew, Wellcome Trust/DBT India Alliance Fellow

But What Makes RMS so Aggressive?

They found that a protein called SPRY2 interacts with MET in development of RMS. This engagement stabilises the MET protein and the stability in turn, is responsible for making the tumor highly aggressive.

Based on our study, MET, SPRY2 and other proteins that interact with these, could be interesting candidates for RMS therapy.
Sam Mathew, Wellcome Trust/DBT India Alliance Fellow

Targetted Therapy

Apart from surgery to remove the tumour, chemotherapy and radiotherapy, new treatment strategies have come up on the radar.
Apart from surgery to remove the tumour, chemotherapy and radiotherapy, new treatment strategies have come up on the radar.
(Photo: iStockphoto)

MET has already been identified as a therapeutic target in numerous cancers. However, the MET pathway plays essential roles in normal cellular function and therefore, targeting it directly could cause undesirable effects on normal cells in the body, he said.

By identifying SPRY2 and its interaction with MET as a crucial aspect that determines MET stability, SPRY2 has emerged as a novel target for RMS therapy. New studies to identify other proteins that are part of the MET-SPRY2 complex could provide additional insights into RMS pathology and therapy.
Sam Mathew

The treatment options for rhabdomyosarcoma depends on the type of RMS, how early it has been detected and the tumor site.

Apart from surgery to remove the tumour, chemotherapy and radiotherapy, new treatment strategies have come up on the radar.

One of the new treatment strategies which is actively being investigated is targeted therapy, where specific pathways that are affected in RMS tumor cells are targeted and brought under control to either kill off the tumor cells or reduce their rate of proliferation and metastasis, says Dr Mathew.

In addition, immune therapy where the patient’s immune system is primed to target the RMS tumor cells is also being studied for potential therapeutic applications.
Sam Mathew

Recording of Childhood Cancer has Gone Up

Leukemia remains the most common pediatric cancer for both sexes.
Leukemia remains the most common pediatric cancer for both sexes.
(Photo: iStockphoto)

Dr Chinnaswamy says there is no clear data that childhood cancers are on the rise in India but because more and more children are being brought in for treatment and getting recording in databases, this adds to the numbers.

Most of the cancers in children are due to a genetic event (in a developing cell) very early in life and unlike adult cancers not due environment, ageing, lifestyle and other issues. Hence, in children we do not expect a rise in cancer occurrence. However, the numbers which are collected by various agencies are increasing.
Girish Chinnaswamy, Pediatric Oncologist, Tata Memorial Centre, Mumbai

According to the National Cancer Registry report for 2012-2014, which collates data from the population-based cancer registries (PBCRs) across India, leukemia remains the most common pediatric cancer for both sexes, followed by lymphoma and central nervous system tumours in males. In girls, CNS tumours exceed lymphomas.

In boys, the relative proportion of childhood cancer was lowest in Nagaland PBCR (north-east region) at 0.7 percent and highest in Delhi PBCR (north region) at 5.4 percent. In girls, it varied from 0.5 percent in East Khasi Hill district PBCR (north-east region) to 3.5 percent in Naharlagun in Arunachal Pradesh (north-east region). 

To keep up with the upsurge in the number of children under treatment, a four-fold jump in pediatric oncologists is needed.

I think we have around 120 pediatric oncologists. Taking into account the number of patients to be treated appropriately, we need at least four times the number. More than oncologists we also need all other specialists too such as pediatric onco-surgeons, bone tumor surgeons, pediatric radiation oncologist, pediatric palliative care, molecular biologist, onco-pathologist.
Girish Chinnaswamy, Pediatric Oncologist, Tata Memorial Centre, Mumbai

In countries like the US, for example, the doctors-to-patient ratio is very different.

The number of dedicated pediatric centres per unit of population is much more. All hospitals are well networked and have a pattern of referral. Insurance cover or government funds take care of funding for children. There are dedicated centres of excellence for doing high-end research and managing complicated cases.
Girish Chinnaswamy, Pediatric Oncologist, Tata Memorial Centre, Mumbai

Batting for more sensitisation among patients and doctors, Chinnaswamy stressed on thrust on pediatric oncology in curriculum in medical school and pediatric post graduate training to manage the burden.

(Sahana Ghosh is a microbiologist-turned-journalist. She writes on science and environment and is interested in science in remote areas.)

(For more news on cancer, follow FIT.)

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Published: 27 Apr 2018, 03:33 AM IST

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