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Harnessing liquid biopsy for cancer precision medicine

Publish Date

23 SEP 2019


Prof. Ilhan Celik MD


As medicine moves toward enhanced precision, where molecularly targeted treatments can be administered to the right patients at the right time, biomarkers are becoming increasingly important.

From the earliest days of medical practice, physicians have turned to various clinical measurements — like height, weight, blood pressure, and heart rate — to assess and monitor patient health. Today, these signs are a mainstay of clinical medicine as are countless others, including sophisticated biochemical readings from blood and other tissues. Such biomarkers can enable clinicians to detect diseases at an early stage, make accurate diagnoses, and follow treatment progress.1

As medicine moves toward enhanced precision, where molecularly targeted treatments can be administered to the right patients at the right time, biomarkers are becoming increasingly important.2 Without them, clinicians cannot determine which treatments are best suited to their patients and must use trial and error — a frustrating scenario in chronic diseases and a potentially life-altering one in cancer, where time can be incredibly precious.3

At Merck KGaA, Darmstadt, Germany, we are harnessing the power of biomarkers to make cancer precision medicine a reality. This includes testing and applying an innovative approach known as liquid biopsy. Unlike conventional tissue biopsies, which often require invasive and painful procedures4, liquid biopsies can be readily obtained, often by drawing a sample of blood. The approach holds promise in cancer — especially lung cancer — where gaining access to tumor tissue can be a major challenge. Importantly, liquid biopsies can capture genetic material from tumors as they grow, making it possible to determine the molecular characteristics of a patient’s cancer prior to and during treatment.5,6

As one example of the potential of liquid biopsies, we recently implemented a genetic test based on the technology. This test, which examines a series of gene mutations, was conducted alongside the traditional method of tissue-based testing as part of a clinical trial in lung cancer. We found that both approaches — liquid biopsy and conventional tissue biopsy — could predict patient response to the clinical trial drug in a comparable manner.7 This represents an important step, not only in how cancer patients can be diagnosed and treated, but also in how we develop and test new potential cancer drugs.

Selection and enrollment of patients in clinical trials — an essential step for any new drug — is often very difficult and complex when based solely on standard tissue biopsies. In fact, the pace of patient enrollment can be so slow that clinical trials last several years and, in some cases, cannot be completed at all. However, we have found that liquid biopsies can significantly accelerate patient enrollment, making it possible to pursue clinical trials of candidate drugs even for relatively small patient populations, including those with rare cancer subtypes.8 Such acceleration can be a real game-changer, enabling the development of much-needed treatments.

With liquid biopsies, we also can analyze hundreds of molecular biomarkers within a single patient sample — each one a potential signal that can help answer important questions: Is a given patient likely to benefit from a particular cancer drug? For patients already undergoing treatment, are their tumors shrinking or not? Are there signs of toxic side effects? Is the current treatment altering the genetics of the tumor, and if so, is there an opportunity for more effective follow-on therapies? 6, 9

Such questions are vital for doctors and patients, but they are also crucial for us here at Merck KGaA, Darmstadt, Germany. By answering them using data from liquid biopsies, we can better guide and accelerate the development of molecularly targeted cancer drugs. That is why the liquid-biopsy-based approach is a cornerstone of our cancer drug development strategy in several key cancers, including lung cancer.  

I believe modern medicine should be able to prescribe the very best treatments based on all available clinical information, giving patients the greatest likelihood of benefit and a good quality of life. We are not there yet, but we are getting closer. Ten years ago, the notion of a liquid biopsy was pure fantasy and now we are seeing its early impact. As a physician and scientist, I am thrilled to witness this progress and to be a part of the team that is driving innovation in cancer drug development at Merck KGaA, Darmstadt, Germany.


  1. Mayeux R. NeuroX 2004;1(2):182-188.
  2. Committee on Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies; Board on Health Care Services; Institute of Medicine; National Academies of Sciences, Engineering, and Medicine; Graig LA, Phillips JK, Moses HL, editors. Washington (DC): National Academies Press (US); 2016 Jun 30.
  3. Duffy MJ et al. Clin Chem 2008;54(11):1770-9.
  4. Marrugo-Ramírez J. Int J Mol Sci. 2018 Oct; 19(10):2877.
  5. Minji L et al. Micromachines (Basel). 2018 Mar; 9(3):100.
  6. Saarenheimo J et al. Front. Oncol. 2019 Mar; 9:129.
  7. Paik P, et al.Phase II study of tepotinib in NSCLC patients with METex14 mutations. In: Proceedings from the American Society of Clinical Oncology; June 3, 2019; Chicago. 9005.
  8. Lustberg M, et al. Cancer J. 2018 Mar-Apr; 24(2): 61–64.
  9. Rossi G et al. Cancer Res 2019 May. doi: 10.1158/0008-5472.CAN-18-3402.


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