Liquid Biopsy: The Future of Non-Invasive Cancer Diagnostics

Cancer diagnosis has in the past required using procedures that included tissue biopsy, where though they are effective, the patient experiences a lot of discomfort. In the last few decades, there have been technological improvements in the medical field, which have seen new techniques being used to diagnose diseases such as liquid biopsy. A liquid biopsy is a noninvasive diagnostic approach that involves bodily fluids in blood, urine, saliva, or cerebrospinal fluid to establish the presence of cancerous cells or tumor-derived genetic materials. This non-invasive approach has several strengths, including the early diagnosis, the possibility of observing the efficiency of the actions undertaken in a real-time manner, and the monitoring of genetic changes in cancers. As the study goes on, liquid biopsy has been established to be of immense benefit in precision medicine, particularly in the diagnosis, prognosis, and treatment of cancer.

What Is Liquid Biopsy?

Liquid biopsy means evaluating the cancer-associated components in the fluid part of the body. For this reason, liquid biopsies are also different from tissue biopsies, which involve taking a tissue sample using surgical instruments or needle techniques, while liquid biopsies can be taken by mere blood samples or other noninvasive techniques. Among all these components of liquid biopsy, ctDNA, CTCs, and EVs, particularly exosomes and cf RNA, are the most frequently investigated components.

These biomarkers are present in the bodily fluids, which can offer the clinicians the necessary information about tumor biology, as well as the early detection of cancer, identification of the mutations in the tumor, and the assessment of the progress and further development without invasive procedures that are, however, required for obtaining the samples. Hence, liquid biopsy is becoming popular as a valuable modality in the treatment of cancer, especially in patients with inaccessible tumors or patients who need to be monitored frequently during therapy.

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Key Components of Liquid Biopsy

Circulating Tumor DNA (ctDNA): CtDNA is the circulating tumor DNA, which is small-sized fragmented DNA released in circulation by malignant cells. As stated earlier, ctDNA harbors mutated genes that are specific to cancer; therefore, ctDNA is useful for the diagnosis and early screening of cancer. It is also capable of identifying mutations relating to tumor development, treatment response, and disease relapse. In addition, the detection of MRD using the ctDNA-based liquid biopsy contributes to valuable information regarding the cancer remission or progression after its treatment.

Circulating Tumor Cells (CTCs): CTCs are intact cancer cells that break away from the primary tumor and circulate in the bloodstream. These cells can be isolated and analyzed to provide information about the molecular characteristics of the tumor, including genetic mutations and protein expression patterns. By identifying CTCs, liquid biopsy enables early detection of metastatic disease and offers a less invasive way to track the spread of cancer throughout the body.

Exosomes: An exosome is one of the small vesicles that act as a transport of proteins as well as mRNAs and microRNAs out of cells, including malignant cells. They transport numerous molecular cargo, including protein, lipids, and nucleic acid; the RNA and the DNA, for instance. Exosomes can therefore be employed in the detection of cancer through examination of their cargo, which are biomarkers of the cancer. Apart from diagnosis, exosome-based liquid biopsies can also retrieve data about the aggressiveness of the tumor as well as the action of treatment.

Cell-Free RNA (cfRNA): Another biomarker that is still in the developmental phase of analysis is cell-free RNA. In cancer patients, cfRNA may be derived from tumor cells and may reflect gene expression alterations that occur during cancer development. Clinicians are therefore able to get information on the tumor and its response to treatment intervention by analyzing the cfRNA.

Applications of Liquid Biopsy in Cancer Diagnosis

Early Detection: Another advantage lies in its very essence; in other words, that alone makes liquid biopsy invaluable—early-stage cancer diagnostics. These maladies often present no signs in their early stages; lung, colorectal, and breast cancers, for instance, manifest themselves in the final stages often. Because ctDNA or CTCs can be identified in blood or other fluids, liquid biopsy can diagnose cancer at the stage when the disease is not yet manifested, which also improves the likelihood of recovery. An ability to detect specific malignancies through liquid biopsy is highly important, particularly for patients with such types of cancer as hepatocellular carcinoma, which has a higher instance of successful treatment in case of early diagnosis.

Real-Time Monitoring of Treatment Response: Conventional techniques in the evaluation of cancer treatment efficacy include CT and MRI scans. Yet, the methods mentioned above do not necessarily allow for identifying changes at the molecular level. Liquid biopsy is less subjective and accurate when it comes to monitoring that kind of response and analyzing the ctDNA or CTC level at different stages of the tumor treatment. For instance, if a patient develops the tumor to a certain therapy, then the liquid biopsy test will show other mutations that cause this kind of resistance, and the clinician can make changes according to that.

Detection of Minimal Residual Disease (MRD): These cancer cells might still exist in the body after surgery or after undergoing chemotherapy, thus the chances of relapse occur. Liquid biopsy enables monitoring for micrometastasis since ctDNA or CTCs can be detected in the bloodstream. These biomarkers can tell a doctor whether the cancer has been eliminated or if there are still active cancer cells within the body and therefore guide doctors in the kind of other treatments or follow-up to consider.

Prognosis and Risk Stratification: Liquid biopsy is also useful in prognosis and risk stratification in certain diseases. Thus, through ctDNA biomarkers, the clinicians get an estimate of the chances of relapse or metastasis of cancer. Besides, liquid biopsy enables the identification of patients with a high risk of occurrence of the disease to receive more intensive treatment or increased surveillance. For example, detectable ctDNA after treatment is a predictor of relapse in colorectal and breast cancer patients.

Guiding Precision Medicine: A recurring theme has been that, in the age of precision medicine, a treatment plan is based on the kind of genetic abnormality found in a patient’s tumor. In this approach, liquid biopsy is important in offering timely information about the genetic mutation of cancer. In the same way, it helps clinicians choose the right therapy that will suit their patients because it’s effective. For instance, through liquid biopsy, one can determine mutations in genes such as EGFR in lung cancer and make use of targeted therapies like TKIs.

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Challenges and Limitations of Liquid Biopsy

However, as stated above, biopsy has its advantages and challenges as follows: There is one major issue that has to do with the sensitivity of this test. Circulating tumor DNA, RNA, or tumor cells that may be released into circulation may be in very low concentration and hence difficult to detect, particularly in early cancer or when the tumor burden is relatively small. The next-generation sequencing (NGS) is progressing with the methods of liquid biopsy as to its sensibility and accuracy; however, it is still vital to advance.

The fourth is the issue of the interpretation of results, which is an important concentration when conducting the research. Evidence of ctDNA or CTCs does not point to the existence of cancer, as these biomarkers may be present in persons with benign diseases. More to the point, many of the biomarkers found through liquid biopsy may not necessarily have clinical relevance, and this will make it hard to know what to do next.

Last but not least, despite its ability to obtain significant data on the genetic makeup of a tumor, liquid biopsy may not cover all aspects of tumor heterogeneity. Subclonal heterogeneity is quite common in tumors, and not all subclonal mutations may be identified in a single liquid biopsy. It can be utilized together with other diagnostic approaches, including tissue biopsy or imaging, for a better understanding of the tumor.

Future Directions for Liquid Biopsy

Seeing that studies on liquid biopsy are still ongoing, future works hold a lot of promise for this diagnostic method. The early stages of liquid biopsy hope to have a higher, more useful detection rate and better cancer diagnostic performance through improvements in detection sensitivity and advanced sequencing technologies.

Besides being used for detecting solid cancer, liquid biopsy is being investigated for its applicability in diagnosing hematological cancer, including leukemia and lymphoma. Scientists are also trying to develop liquid biopsy for early diagnosis of precancerous states as well as for monitoring the cancer progression.

In addition, a liquid biopsy can be highly valuable in managing a cancer patient’s care by providing a mechanism for changing treatment based on the genetic status of the tumor. As more cancer therapies are discovered, liquid biopsy will act as a saving opportunity for the simultaneous identification of the best treatment and, therefore, better patient prognosis.

Conclusion

Liquid biopsy is a rather revolutionary innovation in the sphere of cancer diagnostics. Its use is non-invasive and can assess early cancer, recap patient’s responses to therapy, and guide care according to individual characteristics are some of the benefits that have made it useful to clinicians and patients. However, there is still a long way to go to make these techniques entirely safe and accurate for the diagnosis of cancer, but the ongoing advancements in LS technologies pave a new era in cancer care that will be much more comfortable for the patients.

References

  1. Hu, Y., Zhu, Y., Zhang, W., Lang, J. and Ning, L., 2019. Utility of plasma circBNC2 as a diagnostic biomarker in epithelial ovarian cancer. OncoTargets and therapy, pp.9715-9723.
  2. Aghamir, S.M.K., Heshmat, R., Ebrahimi, M. and Khatami, F., 2020. Liquid biopsy: the unique test for chasing the genetics of solid tumors. Epigenetics insights13, p.2516865720904052.
  3. Yu, J., Wang, M.C., Ding, W.B., Guo, X.G., Xu, J., Xu, Q.G., Yang, Y., Sun, S.H., Liu, J.F., Qin, L.X. and Liu, H., 2019. Plasma Circular RNA Panel to Diagnose Hepatitis B Virus-Related Hepatocellular Carcinoma. bioRxiv, p.576751.
  4. Mathai, R.A., Vidya, R.V.S., Reddy, B.S., Thomas, L., Udupa, K., Kolesar, J. and Rao, M., 2019. Potential utility of liquid biopsy as a diagnostic and prognostic tool for the assessment of solid tumors: implications in the precision oncology. Journal of clinical medicine8(3), p.373.
  5. De Fraipont, F., Gazzeri, S., Cho, W.C. and Eymin, B., 2019. Circular RNAs and RNA splice variants as biomarkers for prognosis and therapeutic response in the liquid biopsies of lung cancer patients. Frontiers in genetics10, p.390.
  6. Pan, B., Qin, J., Liu, X., He, B., Wang, X., Pan, Y., Sun, H., Xu, T., Xu, M., Chen, X. and Xu, X., 2019. Identification of serum exosomal hsa-circ-0004771 as a novel diagnostic biomarker of colorectal cancer. Frontiers in genetics10, p.1096.
  7. Louis, C., Desoteux, M. and Coulouarn, C., 2019. Exosomal circRNAs: new players in the field of cholangiocarcinoma. Clinical science133(21), pp.2239-2244.
  8. Qiao, G.L., Chen, L., Jiang, W.H., Yang, C., Yang, C.M., Song, L.N., Chen, Y., Yan, H.L. and Ma, L.J., 2019. Hsa_circ_0003998 may be used as a new biomarker for the diagnosis and prognosis of hepatocellular carcinoma. OncoTargets and therapy, pp.5849-5860.
  9. Chi, B.J., Zhao, D.M., Liu, L., Yin, X.Z., Wang, F.F., Bi, S., Gui, S.L., Zhou, S.B., Qin, W.B., Wu, D.M. and Wang, S.Q., 2019. Downregulation of hsa_circ_0000285 serves as a prognostic biomarker for bladder cancer and is involved in cisplatin resistance. Neoplasma66(2).
  10. Zhu, K., Niu, L., Wang, J., Wang, Y., Zhou, J., Wang, F., Cheng, Y., Zhang, Q. and Li, H., 2019. Circular RNA hsa_circ_0000885 levels are increased in tissue and serum samples from patients with osteosarcoma. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research25, p.1499.

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