Multi-Cancer Early Detection Through Liquid Biopsies

Cancer is the number 2 leading cause of death in the United States. Cancer is a disease that is caused by mutation mistakes in the DNA of a normal cell that accumulate and ultimately lead to that cell growing uncontrollably. The likelihood of being diagnosed with cancer goes up exponentially with age.

There are four stages of cancer:

• Stage 0: Abnormal cells are present, but have not spread to nearby tissue. This is called carcinoma in situ CIS. CIS is not cancer, but it may become cancer.

  
  

• Stage I, Stage II, & Stage III: Cancer is present. The higher the humber, the larger the cancer tumor and the more it has spread into nearby tissues.

  
  

• Stage IV: The cancer has spread to distant parts of the body. This is ultimately what ends up killing patients.
  
  

If the cancer is localized, a surgeon or radiation oncologist can cure the patient. But, once the cancer has spread to many places in the body, it can’t be removed and/or you can’t radiate it (i.e. chemotherapy). Patients diagnosed with early-stage cancer have an 80% survival-rate; patients diagnosed with late-stage cancer have a 20% survival-rate.

This makes early detection (and early treatment) critical for improving outcomes.

How We Screen for Cancer Today

There are many ways to screen for cancer, but most are focused on a single type of cancer. Some examples include:

• Colorectal cancer → colonoscopy

  
  

• Breast cancer → mammography

  
  

• Lung cancer → low-dose CT scan

  
  

• Cervical cancer → pap test

  
  

• Liver cancer → liver ultrasound
  
  

Full Body MRIs are able to scan for cancer in up to 13 different organs. That said, full body MRIs tend to be fairly time consuming and expensive; they typically take about an hour to complete at a specialized facility and cost approximately $2,000 $2,500 per scan. Direct-to-consumer offerings include Ezra, Prenuvo, and Halo.

CT scans and PET scans also screen for many types of cancer, but introduce radiation (often making the “risk worth more than the reward” for otherwise healthy patients).

Liquid Biopsies The Future of Cancer Screening

Liquid biopsies, also known as multi-cancer early detection MCED tests, are tests that measure biomarkers in the blood to look for more than 50 different types of cancer – all from a routine blood draw.

Liquid biopsies work by analyzing various biomarkers in the blood, including:

• DNA fragments, including circulating tumor DNA (ctDNA)

  
  

• DNA methylation patterns (chemical changes to DNA that regulate which genes are expressed)

  
  

• Changes in DNA and/or RNA sequences

  
  

• Antibodies that a person may develop against components of growing cancer cells

  
  

• Levels of protein biomarkers

Extensive efforts are currently underway to be able to detect new biomarkers in the blood and to extract more information out of the biomarkers we already have. As with most emerging technologies, we expect liquid biopsies to improve rapidly (i.e. how many cancers can be detected and how early those cancers can be detected) over the next 3-to-10 years.

Liquid Biopsy Landscape

GRAIL (https://grail.com/)

• GRAIL develops the Galleri test, a liquid biopsy that looks at abnormal methylation patterns in circulating fragments of DNA.

  
  

• If cancer is found, GRAIL also predicts the organ where cancer is present also by looking at the DNA’s methylation patterns.

  
  

• Across all stages of cancer, GRAIL’s sensitivity is approximately 50%, with a specificity of 99% (this means GRAIL returns a false negative for 50% of people with cancer).

  
  

• For early-stage cancers, GRAIL’s sensitivity is only 20% (GRAIL’s sensitivity for stage I lung cancer, the leading cause of cancer death in the US, is 5% or less based on data that’s been presented).

  
  

• Galleri’s low test sensitivity means GRAIL currently does not detect early-stage cancer very well.

  
  

• That said, liquid biopsy technology is getting better every year and we expect GRAIL’s sensitivity to improve with time.

  
  

• GRAIL’s Galleri test is not currently approved by the FDA, but they are preparing to file for approval.

  
  

• GRAIL’s Galleri test must be ordered by a physician and typically costs about $1,000.

  
  

• GRAIL raised $2B from investors and was acquired in 2021 by Illumina for $8B.

Freenome (https://freenome.com/)

• Freenome uses a “multiomics” approach that analyzes fragments of DNA, RNA, proteins, and other biomarkers circulating in the blood.

  
  

• Freenome runs machine learning algorithms to look for blood biomarker patterns that resemble those of known cancer patients.

  
  

• Freenome is initially focused on early detection of colorectal cancer (eliminating the need for a colonoscopy). Colorectal cancer is the 2nd leading cause of cancer death in the US.

  
  

• Freenome does not currently have a test available on the market, but their colorectal cancer test is undergoing clinical trials.

  
  

• Freenome is also actively developing a test for pancreatic cancer. (Pancreatic cancer is the 3rd leading cause of cancer death in the US and is usually symptomless until later stages).

  
  

• Freenome has raised $1.1B from investors and remains a private company.

Other companies who have developed (or are developing) liquid biopsies for cancer screening include: Guardant, FoundationOne, CellSearch, Exact Science, and Natera.