Projects

Contents

[^circos]

The project has two components. In the first part of the course, you are asked to submit a project proposal. This will detail the topic and scope of your project. There is great latitutde for choosing a specific topic; some examples are provided below to inspire your choice. The project proposal is worth \(5\%\) of your grade. The purpose of the project proposal is to get you thinking early about a topic that interests you so that you can add to your project as the semester progresses.

The final project is worth 20% and will be due near the end of term.

Project Proposal

You are encouraged to think broadly when chosing a project topic. The topic may be of special interest to you given your previous studies or your background. The topic might also reflect a personal experience or type of cancer that has affected your life in some way. The following structure should help you determine teh suitability of your idea as you try to address the issues below.

– The proposal, which should be no more than 1 page (11pt font), should address the following items (please include subsection headers):

– Summary of Topic: 1-3 sentences that summarizes the topic and scope of your project

– Type to Cancer: 1 paragraph that explains what type of cancer you will focus on (tissue or subtype or special restricted class of tumors). For example, you may be interested in early breast cancer. It may be that your topic applies to multiple cancers, in which case explain why. For example, you might be interested in the role of hypoxia across all solid tumors.

– Molecular genetics: 1 paragraph that explains the molecular genetics of your topic. For example, if your topic is about hypoxia in solid tumors, you might briefly survey what is known regarding genes and gene products central to this response. Or, for example, if you were interested in early breast cancer, you might be interested in the molecular components that control the swtich from in situ to invasive disease.

– Fundamental goal and question: 1 paragraph that explains what you propose to investigate. Here you might add one or two references that you have already found (e.g. a review article) that will form the start of your investigations. Or perhaps you plan to use public databases for your investigation. What do you intend to survey in your project? For example, perhaps you would like to survey if and how the molecular components of hypoxia change across different solid tumor types. Or you may have a specific question that you would like to answer.

– Methods/Scope: 1 paragraph that estimates the end point of your project, how you will go about it, and the level of depth you hope to achieve.

We suggest you also read the next section to get an idea of what is expected in your full project document. The project proposal is supposed to help you decide the questions you will examine.

Full Project

– No specific page length.

– A mixture of media can be used including text documents (eg Google Docs), images (eg Google Drawings), Markdown or other tools that allow you to integrate text with images and videos (as needed). You are encouraged to use modern means to express research and to do so in perhaps a hybrid fashion somewhere between a written paper (primarily text with a few figures) and a presentation (primary figures with sparse text). It is up to you but please make sure that the key concepts are expressed clearly and that the document is well organized.

– Although it is important to have some translational and clinical aspects in your presentation (they provide nice context), don’t forget that our primary focus in this course is on the molecular and genetic components of cancer.

– Consider relating the molecular genetics of your topic back to the hallmarks of cancer and explain how they fit in (or do not fit in).

– Also try to identify the main genes, gene products, epigenetic events relevant to your topic. How do these objects interact or regulate each other?

– Likewise, try to identify the main cellular pathways, responses and processes relevant to your topic.

– Likewise, try to identify the main micro- and macro-environmental components relevant to your topic.

– If you are focusing on a gene or gene product, explain what cancers it is most or least relevant for and why.

– Try to provide the reader with some perspective of the state-of-the-art with respect to your topic. What is known? What is not yet known?

– Comment on the types of model organisms that are used currently. What are their respective limitations and benefits?

– Try to comment on technological aspects of your topic. For example, if you are studying an immune response in live cancer, explain if and how it is possible to measure this specific immune response in a tissue. Are there new exciting technologies that promise big breakthroughs?

These points are suggestions and may not be appropriate for your particular topic. The project proposal is supposed to help you plan early and identify the key questions you can investigate.

Some Suggestions

¹

The following are some possible projects. Feel free to choose one or develop your own topic.

– Immuno-therapies. You may want to pick one specific immunotherapy, a class of immunotherapies or survey all immunotherapies for one or more cancer type. Here you could explain how they work (or do not work as the case may be), where they are most successful, and the direction of this field of research.

– The immunomodulatory role of T-cells in a specific cancer type or cancer types. Similar to above, focusing on inter-cellular signalling, mechanism, limitations, etc.

– Similar to above, other types of immune components or the patient systemic response?

– Or alternatively, what is the role of the tumor microenvironment in the development of a specific cancer or cancers?

– Synthetic lethality and drug design. This is an example of a project that does not focus on a specific gene or process but instead focuses on molecular concepts of epistatsis, synergy and synthetic lethality. Here you would investigate where, how, why these concepts could be used to design novel cancer therapies.

– Epigenetics plays interesting roles in childhood cancers. A project topic like this could survey what is and isn’t know regarding epigenetic events in the development of a specific cancer or across different classes of cancers.

– Gene panel classifiers. For example, Oncotype DX is a clinical assay that measures the (mRNA) expression of 21 genes to predict breast cancer patient benefit from chemotherapy. Your project could investigate the molecular processes represented by the 21 genes and comment on why it works. There are other classifiers (e.g. Mammoprint, Prosignia) across a range of cancers (e.g. prostate, ovarian).

– The molecular basis of BRCA1/2 testing. Here you could explain why women are profiled for BRCA1/2 mutations, the different BRCA1/2 mutations and how they effect BRCA1/2 function. Other genes for other cancers are possible. You could also look across different cancers were the same genes are used.

– Similar to the BRCA1/2 suggestion, there are now several cancer gene panels for different types of cancers with different purposes. For example, Jacques Simard at Laval University has a gene panel to identify women at elevated risk of breast cancer. An investigation of the genes, their relationship to the hallmarks of cancer and their molecular function would be an interesting project.

– The role of any hallmark in a specific type of cancer (too general to cover all cancers; select a specific type of cancer and cover what is known in detail)

– The role of any specific RTK in the development of a specific cancer. This should give a very detailed perspective of the mechanics

• The role of any specific transcription factor in a specific cancer. Here the focus would be on the genes that it controls (and what controls it), how it activates etc.

– The role of a specific drug in a specific cancer. For example, how do anti-angiogenic compounds inhibit tumor growth, what are the problems with these drugs and what is happening at the molecular level.

– A new technology (e.g. single cell spatial profiling) and how it has impacted our knowledge of tissue organization. Please choose technologies that inform on the molecular status of genes or gene products.

– Similarly, multi-modal single cell profiling to study cancer.

– New technologies in pathology and computational pathology for profiling tumors at the molecular level. Please choose technologies that inform on the molecular status of genes or gene products.

– A new type of model system (e.g. artifical tissues). (But try to keep the presentation focused on the molecular aspects. For example, focusing on studies that have tested the capacity of such systems to recapitulate human disease at the molecular level.)

– Molecular profiling used to subtype different cancers (e.g. PAM50 for invasive breast carcinoma)

– Deep learning in cancer to identify new drugs. How does it work? How does it use expression of gene and gene products?

– Molecular characteristics of a specific clinicopathological variable (e.g. breast density).

– Is autophagy a cancer hallmark? This could be any process that you would like to argue is also a hallmark.

– Two-hit hypothesis.

– Is the rate of cancer related to genomic architecture? For example, does the degree of paralogy of specific tumor suppressors and/or genomic maintenance genes?

– Tumor sequencing: what has been done to date for a specific cancer or across a panel of cancers and what has been found

– Vaccinations against cancer. How do they work? What are the advantages compared to other therapeutics.

– Novel therapeutic approaches to target cancer

• Cancer is a wound that does not heal (EMT)