Liquid biopsy: A significant breakthrough for non-invasive monitoring of tumors

Over the past 15 years, early diagnosis and personalized therapies have been the primary goal of modern medicine. This has led to the development of increasingly accurate diagnostic tests and the birth of the concept of precision medicine.

Precision medicine aims to provide specific diagnostic and therapeutic approaches for each patient, taking into account their unique characteristics such as genetics, environment, and lifestyle. Precision medicine plays a critical role in oncology, where the disease varies significantly from patient to patient, making it essential to identify the most suitable treatment options for each. 


Liquid biopsy 


To effectively fight a tumor, it’s crucial to understand it thoroughly and monitor its evolution, as each tumor is unique and evolves in unpredictable ways. Precision oncology aims to adopt new tools to capture real-time tumor evolution and guide effective treatments.

An innovative tool in this context is liquid biopsy, which differs from the traditional solid biopsy that analyzes a tissue sample. Instead, liquid biopsy analyzes a body fluid sample, such as blood or urine, and represents a non-invasive tool for analyzing tumor material. With liquid biopsy, it’s possible to monitor the tumor’s evolution over time, define the prognosis, and identify specific tumor mutations that may guide the choice of more appropriate therapy. 

This approach provides a simple, fast, and cost-effective way to monitor the tumor’s status or response to therapy by searching for circulating tumor cells (CTCs), fragments of circulating tumor DNA (ctDNA), and other analytes circulating in body fluids. 

Liquid biopsy has evident advantages over tissue biopsy, making it an extremely useful tool. 

  • Firstly, liquid biopsy is less invasive, making it a viable option when obtaining tumor tissue is not possible due to the risk of bleeding or difficult access to the site. Tissue biopsy may also cause side effects such as perforations or bleeding. On the contrary, body fluids are easier to obtain.
  • Furthermore, liquid biopsy provides a more representative and complete picture of the tumor as it can identify and analyze DNA from all tumor cells. In comparison, solid biopsy only takes a small portion of tissue and may not be representative of the whole tumor’s diversity.
  • Liquid biopsy can be repeated over time, allowing for the monitoring of tumor evolution. The genetic makeup of tumor cells is highly unstable and susceptible to continuous changes. Through liquid biopsy, it’s possible to track changes in the tumor over time, establish the progression of the disease, and determine the response to therapy in real-time. 


Liquid biopsy tests: Circulating Tumor Cells and Circulating Tumor DNA, innovative diagnostic tools


Circulating tumor cells (CTCs) and Circulating Tumor DNA (ctDNA) are two of the most promising liquid biopsy tests available, analyzing the material released into peripheral blood from the primary tumor and/or metastatic lesions.


  • Study of Circulating Tumor Cells (CTCs)

Circulating Tumor Cells (CTCs) are cells that are released from the primary tumor or metastatic sites and can travel through the bloodstream to other organs, providing valuable information about the tumor’s composition, invasiveness, and response to therapy. Analyzing CTCs has great potential as it reflects the tumor’s real-time progression and variability. CTCs have already demonstrated prognostic value in numerous clinical studies, and their presence in the blood can indicate disease prognosis in metastatic breast, prostate, and colorectal tumors.
Furthermore, studying the genetic profile of CTCs may be useful in identifying therapeutic targets and predicting response to therapies, and several research efforts are currently underway in this direction.
Isolating and analyzing CTCs is technically challenging because these cells are extremely rare in the blood. Innovative technologies have been developed in recent years to overcome this challenge, and progress in this field is ongoing.


  • Study of Circulating Tumor DNA (ctDNA)

Circulating Tumor DNA (ctDNA) is an important biomarker that can be released into the blood from various sources such as primary tumors, CTCs, micrometastases, or metastases. ctDNA primarily originates from tumor cells undergoing cell death, resulting in the release of fragmented DNA into the blood. It has become an integral part of precision oncology as it can be used to identify mutations in the tumor as well as to guide therapy, monitor the disease’s response to treatment, or detect relapses early. 


The use of liquid biopsies: opportunities and challenges


Liquid biopsy tests offer significant potential for advancing precision medicine by enabling access to targeted therapies through biomarker identification and continuous monitoring of the disease and response to treatment. With repeatable and non-invasive tests, liquid biopsy holds promise for more targeted and early screenings for all types of tumors, and administration of molecularly targeted therapies in a more precise and effective manner. Ongoing research and innovation aim to obtain increasingly indicative information to develop more specific and targeted therapeutic strategies for all types of tumors.

Analyzing CTCs has a great advantage in that it analyzes intact cells rather than just DNA fragments. This allows the study of the different populations of tumor cells in the same patient, which can help identify those that may develop drug resistance and allow for a more targeted treatment. The main challenge in studying CTCs is the availability of sensitive and standardized technologies that can be used in both research laboratories and clinical diagnostics.

On the other hand, the primary challenge in analyzing ctDNA is increasing its sensitivity to be able to evaluate its presence in early stages of the disease and intervene when the tumor responds better to treatments.

While waiting for the progress in liquid biopsy technologies, prevention should not be forgotten, and oncology screenings remain a fundamental tool that will see in the future the addition of highly innovative tests, such as liquid biopsy.

Menarini’s commitment to oncology is unwavering and concrete. In 2014, the pharmaceutical group acquired Silicon Biosystems, a company based in Bologna, which develops pioneering technologies and solutions for oncology research and advanced diagnostics. Menarini Silicon Biosystems is committed to fighting solid tumors and hematological cancers such as multiple myeloma, and is constantly searching for new solutions to facilitate disease monitoring through liquid biopsy tests. In 2020, Menarini acquired the American company Stemline Therapeutics, thus expanding the development of new and innovative therapies for the benefit of cancer patients, in the name of its core values that always put the patient first.