Medical Physics

Models and Technologies in Cancer Research

Anna Bajek, Bartosz Tylkowski, Anna Bajek, Bartosz Tylkowski

• Publisher: De Gruyter
• Year: 2021
• ISBN:
  9783110662344
• Edition: 1
• Topic: Naturwissenschaften
• Subtopic: Physik

Modern cancer research is a high-tech undertaking, overlapping with many fields in the physical sciences. These include nanotechnology, engineering, immunology, and bioinformatics. This book focuses on the science and technology underlying the diagnosis and treatement of cancer. The authors offer insights into technologies including radiotherapy, modelling, and drug encapsulation.

1 Personalized and targeted therapies

Magdalena WiŘniewska

Department of Oncology and Brachytherapy, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland

Department of Clinical Oncology, Oncology Centre, Bydgoszcz, Poland

Michał WiŘniewski

Outpatient Chemotherapy Department, Oncology Centre, Bydgoszcz, Poland

Marzena A. Lewandowska

Department of Thoracic Surgery and Tumors, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland

Oncology Centre, Bydgoszcz, Poland

Department of Molecular Oncology and Genetics, Innovative Medical Forum Oncology Centre, Bydgoszcz, Poland

ORCID:https://orcid.org/0000-0002-7360-7810

Ludwik Rydygier Collegium Medicum Nicolaus Copernicus University (UMK CM 2018 WL 103 and UMK CM 2020 WL 183)

This article has previously been published in the journal Physical Sciences Reviews. Please cite as: WiŘniewska, M., WiŘniewski, M., Lewandowska, M. A. Personalized and targeted therapies Physical Sciences Reviews [Online] 2021, 6 DOI: 10.1515/psr-2019-0057

Abstract

Biomarker is defined as indicator of normal or pathogenic biological process or response to an intervention or exposure. There are several categories of biomarkers but predictive biomarkers play the most important role in the treatment of neoplasms. In some cancers there may be more than one potential biomarker, and their identification determines the treatment of the patient. Identification of predictive biomarkers allows the development of novel targeted therapies resulting in tailored treatment. In this chapter we discuss most important predictive biomarkers used in contemporary oncology for which there is approved therapies.

Keywords: biomarker, predictive biomarkers, tailored treatment, targeted therapies,

1.1 Introduction

Biomarkers are critical to the rational development of medical diagnostics and therapeutics [1]. Biomarker is defined as indicator of normal or pathogenic biological process or response to an intervention or exposure, according to Food and Drug Administration – National Institute of Health (FDA-NIH) Working Group [2].

There are several categories of biomarkers according to FDA-NIH classification. Predictive biomarkers can be used to identify response to exposure to a therapy or an environmental agent. The response could be a relief of symptoms, improvement in survival, or an adverse effect [2]. Predictive biomarkers are essential to modern personalized therapy in contemporary oncology and are the topic of this chapter. Other categories of biomarkers according to FDA-NIH classification include diagnostic, prognostic, monitoring, safety and pharmacodynamic biomarkers.

1.1.1 Predictive biomarkers

Predictive biomarkers are the most important in the treatment of neoplastic diseases. Their presence allows predicting in which group of patients the therapy will be effective. In some cancers there may be more than one potential biomarker, and their identification determines the treatment of the patient. Table 1.1 represents the broad range of biomarkers, which are analyzed in non–small cell lung cancer to qualify patient for appropriate therapy. There are also biomarkers whose presence is associated with the effectiveness of a given therapy regardless of the type of tumor (so-called organ-independent biomarkers), examples of such biomarkers are mutations in the NTRK or high levels of MSI. In this chapter, predictive biomarkers for which there are approved therapies in the treatment of solid tumors will be discussed.

Table 1.1:Predictive biomarkers in non-small cell lung cancer.

Disease	Biomarker	Drug
Non-small cell lung cancer	EGFR	Erlotinib
		Gefitinib
		Osimertinib
		Afatinib
		Dacomotinib
	ALK	Crizotinib
		Ceritinib
		Lorlatinib
		Alectinib
		Brigantinib
	ROS1	Crizotinib
		Ceritinib
		Lorlatinib
		Alectinib
		Brigantinib
	BRAF	Dabrafenib
		Vumurafenib
	MEK	Capmatinib
	RET	Selpercatinib
	PD-L1	Pembrolizumab
	NTRK	Entrectinib
		Larotrektinib
	No biomarker	Chemotherapy

1.1.2 Diagnostic biomarker

Diagnostic biomarker is used as an indicator of a presence of a disease or condition to assess a subtype of the disease, e.g. profiling of gene expression may be used to distinguish subgroups of patients with diffuse large B-cell lymphoma and different gene signatures of malignant cells. Another example of diagnostic biomarker could be measurement of glomerular filtration rate [GFR] in diagnosis of patients with chronic kidney disease [3, 4].

1.1.3 Monitoring biomarker

Monitoring biomarker is an indicator of disease or medical condition status. It may also indicate an effect of a drug of environmental factor. Examples of monitoring biomarkers are prostate-specific antigen (PSA) in patients with prostate cancer or cancer antigen 125 (CA 125) in patients with ovarian cancer. Both biomarkers are used to assess disease status or burden [5, 6].

1.1.4 Risk (screening) biomarkers

Risk (screening) biomarkers indicate the potential for developing a disease or medical condition in an individual who does not currently have clinically apparent disease or the medical condition. Example of risk biomarkers are mutations in genes related to increased risk of developing cancer as BRCA 1/2 (Breast Cancer genes 1 and 2) mutations which are inked with breast cancer [7, 8].

1.1.5 Pharmacodynamic (response) biomarkers

Pharmacodynamic (response) biomarkers indicate a biological response that may be seen in a patient treated with a drug or an environmental factor. Example of a such biomarker is a standardized uptake value (SUV) measured by PET/CT (Positon Emission Tomography/Computed Tomography) with 18-FG-glucose marked contrast, used as a response biomarker when assessing a response in a patients treated with chemotherapy for diffuse large B-cell lymphoma or Hodgkin lymphoma [9, 10].

1.1.6 Safety biomarker

Safety biomarker is measured for determining a risk of toxicity or an adverse effect. It may be assessed after or before an exposure to a drug or an environmental factor. Safety biomarker example cloud be a serum creatinine for monitoring renal toxicity in a patients treated with a potentially...