Despite cancer is still one of the most challenging threats of the XXI century, in the last decades we have witnessed a great improvement both in diagnosis methods and treatments. Nowadays many cancer types, including some of the traditionally considered as more aggressive such as colon or breast cancer, have a specific screening method that permits an early detection of tumors. Big efforts in research and development have led to the identification of the so-called biomarkers or new image tools that can identify a small tumor even before patients start to manifest symptoms. It is undoubtable that all these improvements have a significant contribution to the increase of cancer patients’ survival. However, this progress in diagnosis and screening methods has gone hand by hand with the discovery and improvement of cancer treatments. Therapies are more and more specific, and it is every day more common to see how aggressive and uncomfortable treatments are being substituted by more effective new medicines and with fewer side effects. In this scenario, one tends to wonder which steps and milestones would be next in the management of cancer. Along this post we will talk about the state of the art and the near future of cancer diagnosis and treatment.

Cancer Diagnosis

Why waiting to have symptoms? It is known that most of the times, tumor development starts as a silent disease and shows symptoms when the tumor mass acquires a certain volume or is affecting the normal function of the origin organ. Hence, the challenge is clear: we should be able to detect these malign tumors before symptoms onset. Today, we will focus on three aspects of cancer diagnosis: tumor biomarkers, liquid biopsy and imaging.

  • Tumor biomarkers. As we already explained in a previous post, tumor biomarkers are molecules that change their concentration or original state during the development of a pathology.  Efforts in this field have been done in two directions: on the one hand, the research and description of new tumor biomarkers, and on the other hand, the development of new tools or methods that could accurately detect the changes or presence of biomarkers. These efforts have achieved the implementation of poor-invasive practices, such as a blood analysis, aimed either to detect the development of a new tumor or, most frequently, to detect the relapse in patients previously diagnosed from cancer. Nevertheless, this success in research and development has led to a new controversy: the overdiagnosis. Overdiagnosis occurs when tumor biomarkers indicate the presence of a new lesion that would have never required any medical intervention in the lifetime of the patient. This fact has prompted for instance an increase of prostate cancer in most developed counties (where a screening method is available for healthy men).
  • Screening cancer using radiographic imaging is a common practice in western countries. One example is the mammography that is done to the average risk, asymptomatic general population in order to detect breast cancer at an early stage. In the last years screening methods using image tools have been extended to colorectal cancer and lung cancer. In this case, the controversy is set in the decision of which part of the population should undergo this screening and how often. If the entire population is set for a screening method it will be common to have overdiagnosed cases as it happened with the tumor biomarkers.
  • Probably the most revolutionary diagnosis method is the liquid biopsy. Once a tumor is found a biopsy is performed in order to characterize it. However, the biopsy represents just a small portion of the tumor and thus, just a part of the tumor heterogeneity is analyzed which can lead to unreliable results. Moreover, tumor localization can sometimes be a problem to acquire a biopsy. Additionally, serial follow up of tumor progression could be recommended but not easily feasible with tumor biopsies. There is a strong need of less-invasive strategies to get tumor material that allow a real-time monitoring and diagnosis of the disease. It was not so long ago described that some tumor cells detach from the primary tumor and travel through the blood vessels with an average lifetime of 1-2,4 h. These cells are called Circulating Tumor Cells (CTCs) and the development of new methods have allowed their isolation from the other blood components. Liquid biopsy is now extended to the isolation and analysis of other tumor components that could be found in the blood or other body effluents such as free nucleic acids (DNA, mRNA, non-coding RNA…) or vesicles such as exosomes.

However, early detection should always be together with an accurate diagnosis. Defining the tumor type and its features is crucial to select the right treatment and, therefore, it has a clear impact on patient’s prognosis. Traditionally, after tumors are biopsied, they are personally observed under the microscope by a pathologist. Additionally, molecular techniques such as immunohistochemistry or PCR help pathologist to quantify a pre-selected group of biomarkers. All this information serves to make a diagnosis and decide the most suitable treatment. Despite, digital scanners are nowadays helping to automatically quantify biomarkers, diagnosis methods should move one step forward and rely on the activity and functionality of those biomarkers instead of their number. Recent studies have shown that tumor cells could express many inactive proteins, and on the other hand, poor expressed proteins could be very active in tumor cells. Thereby, using a diagnosis method able to quantify both the number and the activation status of tumor markers, such as our platform QR-Pro®, is a next step that should become a worldwide reality in the next years. 

REFERENCES

  • Poulet G, Massias J, Taly V. Liquid Biopsy: General Concepts. Acta Cytol. 2019;63(6):449-455. doi: 10.1159/000499337. Epub 2019 May 15. PMID: 31091522.
  • Sánchez-Magraner L, Miles J, Baker CL, Applebee CJ, Lee DJ, Elsheikh S, Lashin S, Withers K, Watts AG, Parry R, Edmead C, Lopez JI, Mehta R, Italiano A, Ward SG, Parker PJ, Larijani B. High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment. Cancer Res. 2020 Oct 1;80(19):4244-4257. doi: 10.1158/0008-5472.CAN-20-1117. Epub 2020 Aug 27. PMID: 32855204.
  • Schiffman JD, Fisher PG, Gibbs P. Early detection of cancer: past, present, and future. Am Soc Clin Oncol Educ Book. 2015:57-65. doi: 10.14694/EdBook_AM.2015.35.57. PMID: 25993143.