What tumors eat -- and how to poison them | Dr. Christal Sohl | TEDxTulsaCC

Summary

The speaker shares a personal journey of researching cancer, sparked by their aunt's breast cancer diagnosis. They discuss precision medicine, specifically in relation to HER2-positive breast cancer and the difference between traditional chemotherapy and targeted therapies. The speaker explores tumor drivers and cancer metabolism, focusing on the mutation of IDH proteins that can promote tumor growth. Their lab work aims to understand these metabolic changes and develop selective therapies. The emotional connection to the research is highlighted through personal stories, underscoring the urgency and motivation to combat cancer.

Takeaways

• 😀 The speaker's personal motivation for cancer research stems from their aunt Lizzie's diagnosis with breast cancer, highlighting the emotional drive behind scientific work.
• 😀 The breast cancer subtype discussed, HER2-positive, represents one of the earliest examples of precision medicine in cancer treatment, with Herceptin being a key example.
• 😀 Precision medicine in cancer is compared to a more targeted approach, unlike traditional chemotherapy, which can be likened to spraying a field with a crop duster.
• 😀 Cancer treatment is complicated because, although we can identify tumor drivers, not all therapies are effective, and patients may relapse despite initially responding to treatment.
• 😀 The research focuses on understanding tumor drivers, which result from genetic mutations, deletions, or amplifications in cancer cells.
• 😀 Tumor cells have a unique metabolism that enables them to grow and divide rapidly, utilizing not just glucose but other building blocks like glutamine and serine for energy.
• 😀 One of the key proteins studied in the speaker's lab is Isocitrate Dehydrogenase (IDH), which plays a critical role in cellular metabolism and cancer development.
• 😀 Mutations in IDH can lead to the production of a carcinogenic metabolite, which contributes to a pro-tumor environment, making it a potential target for therapeutic intervention.
• 😀 The challenge in targeting tumor metabolism is ensuring selectivity, as normal cells also require similar metabolic pathways, but some mutations (like IDH) create a specific vulnerability in cancer cells.
• 😀 A breakthrough therapy has been developed that selectively targets the mutant IDH enzyme, showing the potential for precise cancer treatments that directly address the mutation responsible for tumor growth.
• 😀 Despite promising progress, there are rare mutations, like the one found in the speaker's research, that are still not well-targeted by current therapies, underscoring the need for further research and innovation in cancer treatment.

Q & A

What inspired the speaker to start researching how tumors grow and develop?

The speaker was inspired to start researching cancer after their Aunt Lizzie was diagnosed with breast cancer, which motivated them to learn everything they could about treatment strategies and cancer mechanisms.

What is Her2-positive breast cancer, and why is it significant in cancer research?

Her2-positive breast cancer is a subtype of breast cancer characterized by the overexpression of the Her2 protein. It is significant because it was one of the earliest cancer subtypes to have a precision medicine developed for it, specifically Herceptin, which targets the Her2 protein.

How does precision medicine differ from traditional chemotherapy in cancer treatment?

Precision medicine targets specific tumor characteristics, like genetic mutations or overactive proteins, to selectively destroy cancer cells, while traditional chemotherapy works by targeting and killing rapidly dividing cells, but it is less selective and can affect healthy cells as well.

What is the challenge in distinguishing between cancer cells and healthy cells in cancer treatment?

The challenge lies in the fact that cancer cells often look similar to healthy cells, making it difficult to target only the cancerous ones without affecting normal tissues. Even when cancer cells have distinct mutations, there are still challenges in targeting them effectively without harming healthy cells.

What are tumor drivers, and how do they contribute to cancer development?

Tumor drivers are genetic mutations or alterations that push cells to grow uncontrollably. These drivers can include mutations in proteins that promote cell growth and division, or in metabolic pathways that allow tumors to thrive and expand.

Why are tumor drivers considered both a superpower and an Achilles' heel for cancer cells?

Tumor drivers are considered a superpower because they enable cancer cells to grow rapidly and aggressively. However, they are also an Achilles' heel because cancer cells become highly dependent on these drivers, making them vulnerable to targeted therapies that can shut down the specific pathways they rely on.

What is the significance of tumor metabolism in cancer research?

Tumor metabolism is significant because cancer cells often alter their metabolic processes to fuel rapid growth and division. These changes in how tumors consume and process nutrients, like glucose, glutamine, and serine, can present vulnerabilities that might be targeted in precision medicine.

What role does isocitrate dehydrogenase (IDH) play in tumor metabolism?

IDH is a crucial enzyme in tumor metabolism, as it helps regulate important metabolites needed for various cellular reactions. Mutations in IDH can disrupt its normal function, causing it to produce harmful metabolites that support tumor growth and contribute to cancer progression.

How do mutations in IDH contribute to cancer development?

Mutations in IDH cause the enzyme to acquire a new, harmful function that leads to the production of a carcinogenic metabolite. This metabolite creates a pro-tumor environment, supporting cancer growth and making the tumor more aggressive.

What are the potential therapeutic implications of targeting IDH mutations in cancer treatment?

Targeting IDH mutations offers a promising therapeutic approach, as small molecules can be designed to selectively inhibit the mutant enzyme, reducing its harmful activity. This strategy has already led to the development of drugs that selectively target IDH mutations, benefiting patients with specific types of cancer.