A Student’s Venture into the Real World of Science

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By: Jennifer Guan
Supervisor: Dr. Sunit Das

This past summer I had the opportunity to be a part of the Das lab at Sick Kids Hospital. Needless to say, I felt excited and lucky to be able to learn concepts and techniques in real life, and see how they compare to the colourful illustrations that textbooks so charmingly depict.

One of the lab’s areas of focus is on glioblastoma multiforme (GBM), one of the most aggressive primary brain tumours in children and young adults. Diagnosis has become a death sentence, as even with surgical removal of the tumour, radiation, and chemotherapy, the cancer returns and average survival is just one year. Resistance to temozolomide (TMZ), a first-line chemotherapeutic for this malignancy, is largely due to glioblastoma stem cells (GSC).1 Linked to this resistance and stemness is the protein, inhibitor of DNA binding 1 (ID1).2 This raised interest in decreasing ID1 expression to enhance drug effect.

An FDA approved drug that is currently being used to treat psychosis, promotes ID1 degradation and causes cytotoxicity in some cell types. We decided to test this in our study and see if the same phenomenon would be seen in the GSC lines. A few weeks of cell culture and Western Blot analysis confirmed the drug’s prevalent effect and we began to treat cells with the drug in addition to TMZ.

We found that with drug alone, the cells’ ability to form spheres (indicative of tumour forming capacity) is decreased. Even more promising, we saw that combination treatments inhibited cell proliferation when compared to the control and each treatment alone. On the protein level, we saw that markers for resistance and proliferation were both completely knocked down with the combination treatment, even when the lowest dosages of both drugs were used.

Since ID1 is degraded, otherwise resistant cells are sensitized to TMZ. This powerful concoction allows a lower TMZ dosage to be just as effective. With a longer time to tumour recurrence and decreased drug toxicity, GBM patients are provided with a new therapeutic potential that will hopefully improve their quality of life. Although there are still many future steps to take, because this drug is well-recognized, the path to providing patients with this treatment will be very feasible.

This summer experience has been both interesting and fun, and it’s certainly left an indelible imprint that only the nuisance of mysteriously dying cells can leave. I’ve seen that scientific research, even on the smallest scale performed by yours truly, takes great patience and resolve. Some days, everything is perfect and you fondly add antibodies with joy. Other days, simply nothing works and you wonder what you did to make karma so spiteful. Of course, this is all sprinkled with clumsy errors that are, alas, inevitable to humans. But at the end of it all, when you gather together everything that was done, you cannot help but feel a sliver of pride for the tiny drop of knowledge that you contributed to the quick-flowing, endless river that is science. You know that to be able to help just one person would be worth it.

The details of this experiment will fade in just a few short weeks, but the way I have felt while working with such helpful and easy going lab mates will not. I am grateful to both the Das lab and to IMS for the chance to be a part of this memorable summer. I am encouraged to know that there are so many diligent and selfless scientists, striving to gain insight and knowledge to help improve the lives of others. For all this, I am glad to be a part of science.

References:

1. Clarke MF, Dick JE, Dirks PB, et al. Cancer Stem Cells – Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer res. 2006;66(19):9339-9344.

2. Lasorella A, Benezra R, Iavarone, A. The ID proteins: master regulators of cancer stem cells and tumour aggressiveness. Nature Reviews Cancer. 2014;14(2):77-91.