By: Simran Padam, Medical Director, Medical Affairs
Personalized treatment approaches have emerged as pivotal in improving outcomes for hematological cancers. Central to this advancement are biomarkers, which are measurable indicators that signal biological processes or pathological changes within the body. They play a crucial role in tailoring hematology oncology therapeutic strategies to individual patients and have transformed personalized medicine in oncology.
Heterogeneity in Hematological Cancers
Due to their disease heterogeneity, hematological cancers are well-suited for personalized approaches. As a diverse group of malignancies, they each have several subtypes and states, varying from person to person. Historically, these indications have challenged the one-size-fits-all treatment approach due to patient variability, such as genetic differences in drug metabolism and underlying health conditions.
Hematological cancer cells can also develop resistance to therapies over time, reducing treatment effectiveness. This resistance may occur due to genetic mutations, epigenetic changes, or a tumor’s microenvironment. Fortunately, personalized treatment plans help circumvent therapy resistance while optimizing response rate and improving quality of life.
Importance of Biomarkers in Understanding Oncology Disease Progression
Biomarkers are integral for tracking the progression of hematological cancers, providing essential insights and real-time data into how the disease evolves. Among the types of biomarkers that can help support hematological oncology treatment plans include:
Genetic Biomarkers: Reveal specific mutations that can predispose individuals to certain diseases or influence their response to treatment. FLT3 mutations seen in acute myeloid leukemia (AML) and BCR-ABL1 fusion gene seen in chronic myeloid leukemia (CML) are two examples.
Molecular Biomarkers: Encompass various molecules, such as RNA and metabolites, to reflect the physiological state of the cells and their disease pathways. For example, microRNAs (miRNAs), such as miR-21 and miR-155 have been found to be overexpressed in lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). In addition, measurable residual disease (MRD) detection is widely employed in various hematological malignancies.
Protein-based Biomarkers: Include proteins found in blood, tissues, or other bodily fluids that can indicate disease presence or progression. Protein-based biomarkers are the most widely used biomarkers in cancer screening and diagnosis. For example, CD19, CD20, CD22 found in B-cell lymphomas or CD33 found in AML are protein-based biomarkers.
They can help with the following diagnostic and prognostic advantages:
- Early Detection: Biomarkers can identify cancer cells before symptoms appear or before tumors are visible through imaging.
- Disease Subtyping: Biomarkers assist in classifying the specific type of hematological cancer, which is vital for the appropriate treatment.
- Risk Stratification: Biomarkers can help assess the risk of disease progression or relapse.
- Minimal Residual Disease (MRD) Detection: After initial treatment, some cancer cells may remain undetectable by conventional methods. However, biomarkers can help detect MRD, which helps avoid the risk of relapse.
- Understand Resistance Mechanisms: Biomarkers can help identify mechanisms of resistance to treatments, as mutations in certain genes can alter the effectiveness of targeted therapies.
Recent Advancements in Biomarker Research
The latest advancements in biomarker research have further elevated the biomarker’s role in disease diagnosis, treatment, and monitoring. Undoubtedly, no other oncology discipline incorporates biomarker data more routinely in clinical practice than hematological malignancies to optimize medical care for maximum benefit while minimizing patient risk.
These recent advancements continue to broaden the pool of biomarkers, offering hope for improving patient outcomes via targeted therapies and precision medicine. As a result, these advances have revealed new information about the complex mechanisms that drive carcinogenesis, cancer metabolism, the molecular landscape of cancer, immune evasion, drug resistance, and disease relapse, among other important areas. These developments, combined with targeted therapies, have dramatically improved survival status and quality of life for those diagnosed with hematological cancers.
A few notable developments include:
- Liquid Biopsy Technologies
Liquid biopsy technologies involve analyzing biomarkers from bodily fluids to detect and monitor cancers, offering a non-invasive alternative to traditional biopsies. In hematological cancers, a liquid biopsy can help identify mutations otherwise absent in a tissue biopsy. The analysis of circulating tumor DNA (ctDNA) in a liquid biopsy can also permit genotyping and help monitor the effectiveness of chemotherapy. - High-Throughput CRISPR Screening
High-throughput CRISPR screening techniques provide in-depth information about genetic mutations, structural variations, and copy number alterations in tumors. This approach is utilized in hematology oncology indications to identify novel modular genes for drug efficacy and resistance and new therapeutic targets and synthetic lethal interactions. - Proteomics
Proteomics involves studying the entire set of proteins expressed in a cell or tissue. Proteomic techniques have been increasingly applied to biofluids, including serum, saliva, urine, and cerebrospinal fluid. These biofluid proteomes are a host of clinically relevant biomarkers that help serve as a diagnostic tool for hematological malignancies. - Single-Cell Sequencing
Single-cell sequencing offers insights into tumor heterogeneity by examining individual cells. It reveals differences between tumor cells and normal cells while identifying rare cell populations. Single-cell technologies can be applied in several areas of hematology, including the immune system, tumor cells, therapy resistance, clonal evolution, bone marrow transplants, and more.
Ethical and Integration Considerations
Although biomarkers offer promising potential, integrating them into clinical practice poses some challenges. From an ethical perspective, patients must be fully informed about the implications of biomarker testing, including possible risks, benefits, and the impact of findings on treatment decisions. While biomarkers must undergo rigorous validation and regulatory processes, it’s important to ensure the methods for biomarker testing are consistent and accurate across different laboratories and clinical settings. Additionally, as some biomarker tests rely on genetic data, privacy must be carefully managed.
Developing and implementing biomarker tests can be costly for patients; therefore, we must ensure that these tests are affordable and accessible to patients.
Biomarkers must also be seamlessly integrated into existing practice without causing disruption. Integration necessitates training physicians on these biomarkers and practical guidelines on their use. Although established guidelines and recommendations for specific biomarkers exist, some biomarkers fall outside these parameters, challenging decision-making. Such cases must be discussed in an interdisciplinary molecular tumor board, requiring time-consuming research for board participants and often resulting in disagreements regarding the interpretation of available research.
Biomarker data interpretation can be difficult, particularly for oncology studies. Special tools/programs and expertise may be required. Biomarkers must also have high sensitivity (the rate of detecting true positives) and specificity (the rate of detecting true negatives) to be useful in clinical settings.
Addressing these considerations/challenges will necessitate collaboration among a multidisciplinary team.
Partner with a CRO Experienced in Oncology Biomarkers
From successfully managing the large volume of data from high-throughput technologies to ensuring biomarkers offer real-world clinical benefits, biomarker integration into clinical practice is complex. However, at Worldwide, we have a proven track record of successfully utilizing biomarkers in oncology development. Check out our white paper to learn more about our services, or contact our team to find out how we can help support your oncology drug development program.
