#SROA2020 Highlights Cancer Research Insights: The Last Decade

By Tammy McCausland

Precision medicine, she said, is focused on trying to develop molecular fingerprint of a person’s cancer. It looks at surface receptors, DNA mutations, epigenetic alterations and metabolic changes. Precision medicine can help select the best treatment plan for a patient; it also have predictive powers. However, precision medicine is expensive, time consuming and data intensive.

To accurately capture and model an individual’s cancer, researchers can conduct a genomic analysis then use a fruit fly—a “fly avatar”—and screen for mutations. This modelling can be used for drug screening to find treatments for patients.

Epigenetics, the study of how human behaviors and environment can cause changes that affect the way genes work, can promote cancer. Small DNA/RNA/proteins that build up over time can have a big impact: they can alter how frequently a gene is read and transcribed to make protein and can alter how RNAs (ribonucleic acids) are processed. RNAs provide information that leads to protein production. If you change how RNA gets processed, it affects regulation in the cells, which can result in cancer formation.

Cancer cells have different metabolisms. Metabolism is very complex with many interconnected patterns and processes. Cancer cells have significantly altered metabolisms because they grow and divide rapidly. Targeting metabolism is hard because all cells need these pathways to function. HIF1 (hypoxia-inducible factor 1) promotes breast cancer metastasis and

is a possible drug target. Solid tumors have hypoxic (low oxygen) environments. This is a problem for normal cells, but cancer cells activate genes to solve this problem.

There are four hallmarks of metastasis: motility and invasion; plasticity; modulation of microenvironment; and colonization. The tumor microenvironment aids metastasis. Many cells and signaling molecules aid in “convincing” cells to leave the primary tumor site, and also help the tumor cells “feel at home” in their new location.

Dr. Clarke explained that our immune system is a cell-based system that defends our bodies from infection by recognizing self versus non-self. It recognizes pathogens like bacteria, viruses and tumors. The immune system can recognize tumor cells, but sometimes it doesn’t do it effectively or the tumor cells find ways to hide from the immune system. Immunotherapy’s goal is to use the immune cells to help fight cancer. Immunotherapy treatments can take several forms:

• Stimulate (boost) the immune system so it works harder or smarter to find and attack cancer cells
• Making research products similar to immune system components to aid the immune system’s ability to find and attack cancer cells

For example, use natural killer cells for immunotherapy to remove tumor cells from the body. Natural killer cells can recognize virally infected cells, stressed cells and tumor cells. Natural killer immunotherapy works by increasing the total number of natural killer cells in the body, boosting natural killers to make them stronger or boost the natural killer ability of other cells and recruit them to tumor site to kill the tumor.

Recruiting T-cells to a tumor (e.g., mesenchymal stem cells (MSCs)—the “groupies” of cancer cells) is another immunotherapy approach. The goal is to genetically modify MSCs, so they can recruit T-cells to the tumor site to attack the tumor.

Understanding resistance is a key area of research. Resistance occurs for a number of factors. Researchers study tumor growth, burden and heterogeneity; physical barriers; immune system and the tumor microenvironment; the undruggable genome; and therapeutic pressure.

Dr. Clarke said the American Cancer Society also researches health equity strategies. Health inequities and health disparities may be characterized by age, gender, disability status, ethnicity/race, nativity and immigrant status, geography, income, language, social class or sexual orientation. The ACS aims to generate research studies to understand, identify and/or define modifiable and unjust factors that contribute to or sustain inequity (e.g., resources, access to care, behaviors, quality of care); and lead to a sustained reduction in disparities and/or equitable outcomes in cancer.

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