Sequencing HHMI BioInteractive Cancer Resources
Why don’t we have a cure for cancer? This question arises from a series of misconceptions: that cancer is one disease, caused by one gene that is the same in all people.
To address these misconceptions in my 300-level Cancer Biology course, I’ve found that strategic sequencing of the cancer resources from HHMI BioInteractive can allow students to take basic biology knowledge and combine it with real patient data. Armed with knowledge of a specific cancer pathway, they can evaluate drug efficacy and escape mutants, and then design a gene editing experiment with the possibility of actually curing cancer.
First the basics: for my course, I use the “Eukaryotic Cell Cycle and Cancer” Click and Learn and the accompanying worksheet as a review, but it's also a great way to introduce the cell cycle for the first time. Students click through at their own pace and can immediately see applications for this information as they learn about specific cell cycle regulators that, when mutated, lead to cancer. While exploring the Click & Learn, I have them focus on the question, “Which gene mutations cause cancer?” which transitions into our next activity, analyzing patient data.
When analyzing these data in the form of Gene Cards 1, they see genes they already know from the Click & Learn plus many more. They find that these genes can be grouped both by nascent function and as oncogenes or tumor-suppressor genes, leading them to ask if we can predict which gene mutations cause specific cancers.
They examine data about individual patients’ cancers from the Gene Cards 2 component of the activity; these cards list specific mutations. They find that any given mutation can cause multiple types of cancer and that most cancers result from mutations in many genes. So probably we won’t find a cure for all cancers, but maybe we could find treatments for some that have mutations in specific genes?
At this point, I turn it into a patient case study and pick one gene out of the Gene Cards activities. I go with egfr, since researching the drug mechanism brings up some great information on tyrosine kinases and cell signaling cascades. Students research EGFR and find it is a tyrosine kinase receptor that, when unregulated, causes cell proliferation and other cancer-promoting processes. BioInteractive also has some great resources regarding the oncogene bcr-abl and drugs that target it.
After knowing the molecular mechanism of the EGFR protein, students evaluate the drug gefitinib, identifying how it functions and how specific mutations prevent its function (Figure 2).
This extends to an image analysis activity in which they view authentic fluorescence microscopy data showing drug screens in cell lines (Figure 2). These supplemental materials to the BioInteractive resources can be found in the Cancer Genomics folder at the QUBES Hub.
Finally we come to, “Well, if drugs are not cutting it, how might we treat cancer without them?” They now know the role of a specific protein in a cellular pathway, how a mutation specifically leads to cancer, and how certain mutations can escape drugs.
They’re ready for CRISPR-Cas9! I am so excited that the Click & Learn for CRISPR-Cas9 is now available and I think everyone needs to see it; it explains CRISPR-Cas9 technology thoroughly but accessibly. Armed with this new tool, my students design an experiment (and they actually want to do it!) to “cure cancer.”
The students feel ownership of this semester-long storyline, and I feel good about it as a professor because it has everything you want in a class activity: depth of scientific knowledge, authentic data, active learning, student engagement, real-world applicability, and best of all I didn’t have to design it all from scratch. It's a thing of beauty.
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