How Evolution Is Shaping Cancer Research
2Digest
This podcast, in partnership with Cancer Research UK, delves into the evolutionary nature of cancer. It explains cancer as uncontrolled cell growth that evolves, adapts, and fights back, drawing parallels to Darwin's finches. Tumors are described as complex ecosystems, making eradication difficult. The TracerX study mapped lung cancer evolution, identifying universal mutations. Neoantigens are highlighted as early detection markers and targets for vaccines like LungVax. Research also explores why some individuals are resistant to cancer, studying \"super avoiders\" and animals like whales and naked mole rats. The \"dark genome\" and cellular plasticity in childhood cancers are discussed, along with the role of extrachromosomal DNA (ecDNA). Novel strategies include rewiring cancer cells for self-destruction, CAR T-cell therapy, and a \"Trojan horse\" approach using modified viruses. Finally, the impact of the gut microbiome on cancer immunity and treatment efficacy is explored.
Outlines
The Evolutionary Nature of Cancer and Its Ecosystem
The podcast introduces cancer as an evolving, adaptive entity, akin to a complex ecosystem. It draws parallels to Darwin's observations of divergent evolution and explains how tumors, like diverse species, develop unique survival strategies in response to environmental pressures such as low oxygen or immune surveillance, making them challenging to eradicate.
Mapping Lung Cancer Evolution and Early Detection with Neoantigens
The TracerX study, a large-scale lung cancer evolution project, is detailed, focusing on sequencing DNA to construct evolutionary trees and identify universal mutations. This research connects to the discovery of neoantigens as early indicators of cancer, paving the way for blood tests and preventative vaccines like LungVax.
Natural Cancer Resistance and the Role of the Dark Genome
The discussion explores why some individuals resist cancer, investigating \"super avoiders\" and centenarians. It also examines natural immunity in animals like whales and naked mole rats, and delves into the \"dark genome,\" revealing how cancer can exploit ancient viral DNA within it.
Cellular Plasticity, ECDNA, and Rewiring Cancer for Self-Destruction
This section highlights non-genetic cellular plasticity, particularly in childhood cancers, and the role of extrachromosomal DNA (ecDNA) in cancer cell aggression and drug resistance. A novel strategy of \"rewiring\" cancer cells to induce self-destruction through overstimulation is presented.
Advanced Therapies: CAR T-cell and Trojan Horse Strategies
The podcast explains CAR T-cell therapy, a \"living drug\" approach where a patient's T-cells are engineered to fight cancer. It also introduces the Trojanix strategy, using modified viruses as \"Trojan horses\" to deliver therapeutic genes into tumors for self-destruction.
The Gut Microbiome's Influence on Cancer Immunity
The significant impact of the gut microbiome on the immune system's response to cancer and immunotherapy is discussed. Research into manipulating the gut biome, potentially through capsules, to enhance treatment efficacy is highlighted.
Keywords
Cancer Evolution
Cancer's ability to adapt, respond to its environment, and develop resistance to treatments, mirroring evolutionary principles like natural selection and adaptation to selective pressures.
Tumor Ecosystem
The concept of a tumor not as a uniform mass, but as a complex community of diverse cell types and microenvironments, similar to a natural ecosystem, with various species competing and interacting.
TracerX Study
A large-scale research project focused on mapping the evolutionary history of lung cancer by sequencing patient tumor DNA, aiming to identify key mutations and evolutionary pathways.
Neoantigens
Novel antigens expressed on the surface of cancer cells due to mutations, which can be recognized by the immune system as foreign, serving as targets for cancer vaccines and early detection.
LungVax
A potential vaccine designed to train the immune system to recognize and eliminate pre-cancerous lung cells by targeting specific neoantigens, aiming for early prevention.
Super Avoiders
Individuals who, despite having significant risk factors for cancer, do not develop the disease, offering insights into natural protective mechanisms and potential therapeutic targets.
Dark Genome
The vast majority (98%) of the human genome that does not code for proteins, containing evolutionary relics like viral DNA, which can be reactivated by cancer cells to aid their survival and spread.
Cellular Plasticity
The ability of cells, particularly in young cancer patients, to change their behavior and treatment resistance without immediate genetic mutations, influenced by factors beyond the core genome.
ECDNA (Extrachromosomal DNA)
Rogue, circular DNA molecules found in cancer cells but not healthy cells, enabling rapid division, resistance to treatment, and other aggressive behaviors.
CAR T-cell Therapy
An immunotherapy where a patient's T-cells are genetically engineered to recognize and attack cancer cells, acting as a \"living drug\" for targeted cancer treatment.
Gut Microbiome
The community of microorganisms residing in the digestive tract, which plays a crucial role in immune system function and response to cancer therapies like immunotherapy.
Q&A
How does cancer's ability to evolve make it difficult to treat?
Cancer evolves by adapting to its environment, similar to Darwin's finches. Tumors can develop diverse survival strategies in response to pressures like low oxygen or chemotherapy, leading to resistance and making eradication challenging.
What is the significance of the TracerX study?
The TracerX study mapped lung cancer evolution by sequencing vast amounts of DNA. It identified universal mutations in the \"trunk\" of cancer development, suggesting that targeting these core mutations could be more effective than targeting peripheral ones.
How can neoantigens help in fighting cancer?
Neoantigens are unique markers on cancer cells. Identifying them allows for early detection through blood tests and the development of targeted vaccines like LungVax, which train the immune system to recognize and destroy pre-cancerous cells.
Why is it important to study animals that are resistant to cancer?
Studying cancer-resistant animals like whales and naked mole rats can reveal natural defense mechanisms, such as multiple tumor-suppressing genes. This knowledge could be translated into new human therapies to prevent or treat cancer.
What is the \"dark genome\" and how can cancer exploit it?
The dark genome is the non-coding 98% of DNA, containing ancient viral sequences. Cancer cells can reactivate these sequences to evade immune defenses, promote growth, and spread, essentially using evolutionary relics against the body.
How does CAR T-cell therapy work?
CAR T-cell therapy involves extracting a patient's T-cells, genetically modifying them to recognize cancer cells, and reinfusing them. These engineered cells then actively seek out and destroy cancerous cells, acting as a personalized, living medicine.
What is the Trojan horse strategy in cancer treatment?
This strategy uses modified viruses to deliver cancer-killing agents directly into tumor cells. The virus acts as a Trojan horse, bypassing defenses, and once inside, triggers self-destruction and breaks down the tumor's protective wall, allowing the immune system to attack.
How does the gut microbiome influence cancer treatment?
The gut microbiome significantly impacts the immune system's response to cancer and immunotherapy. Research is exploring how specific microbial compositions can be introduced via capsules to enhance a patient's immune response to cancer.
Show Notes
In this very special episode Michael and Hannah look at some of the groundbreaking, jaw-dropping and hope inspiring projects that Cancer Research UK are supporting right now.
From identifying tiny "flags" cancer cells show to using cancer's own evolution against it, they show why current research today will hopefully mean a better tomorrow for many.
Cancer Research UK are the world's leading cancer charity, supporting research into the ongoing quest to better prevent, detect and treat the disease.
-------------------
For more information about Cancer Research UK, their research, breakthroughs and how you can support them, visit https://cancerresearchuk.org/restisscience
Cancer Research UK is a registered charity in England and Wales (1089464), Scotland (SC041666), the Isle of Man (1103) and Jersey (247). A company limited by guarantee. Registered company in England and Wales (4325234) and the Isle of Man (5713F). Registered address: 2 Redman Place, London, E20 1JQ.
-------------------
Find The Rest Is Science all over the internet by clicking here.
-------------------
Video Producer: Adam Thornton + Oli Oakley
Video & Social: Bex Tyrrell
Assistant Producer: Imee Marriott
Producer: Simona Rata
Head Of Digital: Samuel Oakley
Exec Producer: Neil Fearn
Learn more about your ad choices. Visit podcastchoices.com/adchoices
Table of contents
United States
