Can a blood draw tell you whether you have cancer?

Key Takeaways

• Liquid biopsy is a promising new technology that analyzes blood, urine, or sputum for unique cancer signatures that can confirm both the presence and type of cancer
• Liquid biopsies can detect a wider array of cancers at an earlier stage than traditional screening protocols, and can be used to effectively personalize and monitor cancer treatment
• Limitations exist, particularly around test sensitivity, validation, and accessibility due to cost
• Continued advances are extremely promising, and are likely to radically transform the cancer detection and treatment landscape

The evolution of cancer screening 

When Dr. Georgios Papanicolaou invented the Pap smear in 1928, it marked the first major scientific breakthrough in cancer screening. Though the procedure was not widely adopted until the 1940s^[1], it marked the beginning of decades of advancement in cancer screening technologies. In the intervening decades, screening protocols like mammography, colonoscopy, prostate-specific antigen (PSA) testing, and low-dose computed tomography (LDCT) have become common. However, the lack of precision in many of these tests and their finite range of applications has left a large blind spot in our ability to detect the full range of cancers in their earliest stages.

That soon may change thanks to the rapid advancement of an emerging technology: the liquid biopsy. First introduced in relation to cancer in 2010^[2], the liquid biopsy has rapidly become one of the most promising tools in both cancer treatment and detection.

‍

How do liquid biopsies work?

As cells grow and die, they release fragments of DNA into our bloodstream. These fragments, known as cell-free DNA (cfDNA) are detectable in our blood, and can reveal information about our underlying health^[3]. One common form of cfDNA testing is prenatal testing for birth defects^[4]. 

Tumor cells can also release cfDNA, referred to as circulating tumor DNA (ctDNA). These fragments contain genetic alterations specific to the underlying cancer^[5]. Tumors may also release circulating tumor cells (CTCs) that travel through the bloodstream. Liquid biopsies analyze blood, urine, or sputum samples to detect these cancer-related biomarkers^[6]. 

While blood-based cancer screenings have existed for decades, liquid biopsy has significantly advanced clinicians’ ability to detect early cancers and monitor treatment response. Unlike traditional methodologies, which tend to focus on a single cancer type, liquid biopsies can identify a wide range of specific biomarkers to indicate not only the presence of cancer but the underlying type^[7]. Liquid biopsies can also offer a more comprehensive view of a tumor’s genetic diversity, and indicate the degree of metastasis^[8], information which might not be possible to determine with a tissue biopsy.

‍

The promise: early-stage cancer detection and targeted treatments

There are two primary applications of liquid biopsy: cancer monitoring and cancer detection. The promise of finding deadly cancers earlier, and of using genetic information to home in on the most effective treatments more quickly, has driven significant interest in the emerging technology among patients and clinicians alike.

While some tests are available directly to consumers, the majority are still ordered through physicians. Some of the options currently available to patients include: 

• Guardant360: A comprehensive genetic profile for patients with advanced cancers, this test helps to identify the treatment options most likely to be successful through an expanded panel of biomarkers.^[9]‍
• ^‍FoundationOne Liquid CDx: This “companion diagnostic” test analyzes over 300 genes to help determine the most effective cancer therapies.^[10]   
• ‍Signatera by Natera: A personalized molecular residual disease assay (MRD) to help assess the effectiveness of treatments, determine whether additional treatment is likely to be beneficial, and to identify relapse earlier.^[11]‍
• Galleri test by GRAIL: A multi-cancer early detection (MCED) test that purports to detect over 50 types of cancer–including hard-to-detect cancers such as pancreatic, ovarian, and esophageal–often before they become symptomatic.^[12] 

Additional tests target specific cancer types, particularly in patients who have already received a diagnosis. Several additional applications–including tests that screen via different biomarkers such as platelets and extracellular vesicles (EVs)--are currently in development or clinical trials, and may come to market soon^[13].
‍

‍Limitations

While the science of liquid biopsies is advancing at a rapid pace, challenges to their widespread adoption exist. 

Many cancer biomarkers are difficult to detect, particularly in early-stage cancers, leading to false negative results. Even when a tumor is present, and sometimes when it has metastasized, there’s no guarantee that it will shed any of the markers currently tested for via liquid biopsy^[14]; some cancers shed the types of markers currently available liquid biopsy tests look for much more readily than others. Conversely, benign tumors and other non-cancerous conditions may generate ctDNA, leading to false positive results. These could in turn lead to expensive and potentially risky additional testing.^[15] Additionally, liquid biopsies may not capture the full genetic diversity of a tumor, which can lead to incomplete or inaccurate profiling of the cancer. 

Due to the relatively recent emergence of liquid biopsies, further standardization and validation must occur to establish the clinical utility of the technology across cancer types. Additionally, liquid biopsies (especially those using advanced technologies like next-generation sequencing) can be expensive, limiting their accessibility to all patients. MCEDs in particular–perhaps of the greatest interest to individuals eager to improve their odds of detecting cancer as early as possible–are not generally covered by insurance^[16].

As research progresses, liquid biopsies are expected to play an increasingly vital role in personalized medicine, providing early detection and tailored treatment strategies based on the unique genetic profile of an individual's cancer. Numerous clinical trials are underway for expanded applications, and the technology will likely transform our ability to detect, treat, and monitor cancer. 

While the cost may be a barrier to many at this stage, this technology is a worthwhile addition to your screening regimen. At Catch, we monitor emerging technologies such as liquid biopsy–as well as FDA approvals of new screening and treatment protocols–and keep our users informed in order to allow them to take advantage of the latest medical advancements.  

‍