In the past, patients with a particular cancer type all received the same treatment, but research has shown that tumors have unique features, even within the same cancer type. Now, physicians are increasingly using cancer biomarkers to gain more information about a patient’s tumor to predict the treatment that is most likely to work against their unique cancer.
Cancer biomarkers are biological molecules produced by the body or tumor in a person with cancer. Biomarker testing helps characterize alterations in the tumor. Biomarkers can be DNA, RNA, protein or metabolomic profiles that are specific to the tumor. Testing can include genomic testing to look at the DNA sequence, DNA or RNA tests to look for gene fusions, or tests to measure RNA or protein levels.
Biomarkers can be used for several purposes:
Assess an individual’s risk of developing cancer
Determine an individual’s risk of cancer recurrence
Predict the likelihood that a given therapy will work for a specific patient
Monitor a disease’s progression to determine if a therapy is working
How biomarkers guide targeted therapies
Once biomarkers are identified, the next step is to determine if any of the alterations are actionable – that is, whether there’s a genetic change driving tumor growth that can be targeted with an available drug.
There is a lot of focus on developing new targeted therapy drugs that disrupt key drivers of cancer growth, but not all cancer types currently have identifiable biomarkers. Research has shown that treatment that is led by biomarker testing extends patients’ lives.
“We continue to gain valuable knowledge of the more common genomic alterations and have identified remarkable biomarkers, some of which are gene fusions that truly drive tumor growth,” Meric-Bernstam says. “As we do more in-depth profiling of tumors using RNA and protein analysis, as well as other tools, I am hopeful we can better understand the biology of each tumor, further increasing personalization of therapy options.”
Cancer biomarker research focuses on four areas
Many clinical trials are underway in different areas of biomarker discovery. Beyond identifying new targets and determining their significance, new research is focused on:
Immunotherapy response:Immunotherapy has transformed cancer treatment, but not all patients have the same response. Researchers are identifying biomarkers that can predict immune response to determine which patients benefit from which type of immunotherapy.
Liquid biopsies: Liquid biopsies can assess DNA shed from the tumor, called circulating tumor DNA. A simple blood draw can determine common DNA changes to establish personalized treatment choices; it also can assess whether the tumor is responding and examine how the tumor develops resistance to specific therapies based on new genetic alterations found in repeated blood tests.
Minimal residual disease: This category of biomarker can be measured by liquid biopsy testing done after treatment is completed and there in no detectable disease present following exam and imaging. Minimal residual disease measures remaining disease at the molecular level through blood testing. It may be used to determine which patients would benefit from more aggressive treatment or could be spared such aggressive therapy.
Pharmacodynamic markers: These use a biopsy before and during treatment to observe dynamic molecular changes within the tumor and determine if the drug is acting in the way we expect.
Meric-Bernstam’s team performs molecular profiling and matches patients with early Phase I or Phase II clinical trials to study new targeted drugs based on a tumor’s molecular profile. The goal is to use this testing to choose the best treatment plan for each individual, which may also eventually advance cancer research and treatment for other patients.
Insights from the latest research on cancer biomarkers
Several MD Anderson researchers presented new research focused on cancer biomarker development at the virtual AACR Annual Meeting 2021.
Siqing Fu, M.D., Ph.D., professor in Investigational Cancer Therapeutics, will share results from Phase II research of CCNE1 and Wee1 inhibition at the AACR Annual Meeting 2021 (Abstract 974). CCNE1 amplification is a potential predictive biomarker of chemotherapy resistance, and researchers are studying the effects of targeting inhibition of Wee1 to potentially cause cancer cell death. The drug showed promising clinical activity, and further analysis is continuing to examine potential biomarkers of response.
Amber Johnson, Ph.D., a precision oncology scientist in MD Anderson’s Institute for Personalized Cancer Therapy, is presenting another study at AACR (Abstract 392) which characterized gene variants as actionable, potentially actionable or unknown. The study showed that variants that were labeled as potentially actionable were more likely to be proven actionable.
“We are just at the beginning of precision medicine,” Meric-Bernstam says. “Over the next few years, I am confident we will do more and more in-depth characterization of tumors, advance personalized cancer medicine, identify optimal treatment choices and improve outcomes for our patients.”