During the American Association for Cancer Research/ONS Bench to Bedside session at the 43rd Annual Congress in Washington, DC, Victor Velculescu, MD, PhD, of Johns Hopkins University School of Medicine, and Maura Kadan, RN, MSN, of Personal Genome Diagnostics, dissected the science behind precision oncology, including an understanding of genetic alterations, the use of immunotherapy, and how to advance survival with these clinical breakthroughs.

Kadan began by explaining the basics: “I know this can be intimidating,” she said, “but the more you understand the basics, you’ll better understand results and how this impacts your patients with cancer.” DNA makes RNA, which codes for a protein and tells a cell how to function in the body, she explained. She then discussed the different types of mutations: Germline are those you inherit through family DNA, and somatic are those that occur over time and are more tumor-specific. They body also has suppressor genes that are supported to protect from cancer, she said, but if there is a mutation in this gene, the safety net disappears. Driver mutations, on the other hand, speed up the development of cancer cells.

Cancer is complicated, though, so it is hard to find treatments that work, said Kadan. “We need to find ways to stop cells from acting abnormally and identify the genes that cause cancers so they can be targeted,” she said. But cancer cells are tricky—they do not die, they continue to proliferate and mutate, they try anything to continue growth, and they can go undetected by the immune system, which is supposed to help protect against this very thing. Researchers have identified a number of target genes in the most common cancer types through genomic medicine and sequencing, said Velculescu, and great strides have been made in the past decade, when the understanding and technology were limited.

Velculescu then discussed the difference between immunotherapy and targeted therapy: Immunotherapy uses the patient’s own immune system to target cells. Emerging proof-of-concept data demonstrate that the immune system can eradicate advanced metastatic cancer cells in a subset of patients. Immunotherapy can lead more toward cures, he said, whereas targeted therapies can prolong survival but mostly just temporarily. He also mentioned that the more mutations or higher tumor mutational burden a person has, the chances of identifying a tumor that is recognized by the immune system will increase. Some next-generation sequencing panels are measuring tumor mutational burden to determine those who are more likely to respond to immunotherapies.

He then discussed another area of interest: liquid biopsies conducted via a blood draw to detect circulating tumor DNA. This type of DNA extraction was difficult to analyze for many years, but the technology has greatly improved, he said. “Who wants to keep being biopsied all the time when we can do a simple blood test?” he asked.

Velculescu noted a challenge is that early detection and screening is crucial to improving outcomes. Currently, 14 million people are diagnosed with cancer annually worldwide, with 8 million cancer-related deaths. The majority of new cancer cases are detected at a late stage, despite the improved technology and testing available. If early detection of cancer were to improve, 30%–50% of cancer deaths could be avoided and healthcare and economic costs could be reduced, as early treatment of cancer is two- to four-times less expensive than late treatment. The relative five-year cancer survival rates differ for early and late detection:

  • Colorectal cancer: 90% with early detection, 8% with late detection
  • Breast cancer: 97% with early detection, 21% with late detection
  • Prostate cancer: 96% with early detection, 34% with late detection
  • Melanoma: 96% with early detection, 12% with late detection
  • Cervical cancer: 92% with early detection, 15% with late detection

Velculescu said he hopes the future of cancer care involves a push toward early detection and uses known mutations to personalize therapy.

 

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