06 OCT 2020
In oncology, we hear a lot about precision medicine and targeted therapies. What do those terms mean?
Precision medicine is a term that has emerged in the last 15 or so years, where diagnosis and treatment decisions are made based on the understanding of the individual patient’s disease at the molecular level.
Precision medicine can start at diagnosis and extend to other characteristics of the disease, and based on that information, we create a more individual, or personalized treatment. This of course doesn’t have to be limited to oncology, although it’s a term used very often in oncology.
In oncology, there are three categories of pharmacological treatments: cytotoxic chemotherapy, immunotherapy, and targeted therapy. Targeted therapy is designed to “target” a specific molecular alteration in the cancer.
在肿瘤学中，生物标志物是鉴定疾病内在的生物学特征的一种方式。我们经常将基因突变作为生物标志物与适当的靶向疗法匹配，尽管生物标志物不必与治疗相关联 - 它也可用于了解患者的预后或跟踪对治疗的反应。
What is Next Generation Sequencing (NGS)? How is this testing completed?
What progress has been made in the last 5-10 years in terms of understanding of biomarkers and the ability to identify them?
Since the initial discovery of EGFR mutation being a biomarker in lung cancer to predict response to EGFR inhibitors in 20041,2,我们继续发现新的目标和发展new targeted therapies. With this progress, most of the oncology community at this time is aware that we need gene panels for genetic testing. In large academic cancer centers, we are using Next Generation Sequencing as a standard of care. With the growing use of NGS, the testing platforms have been made more user-friendly so that samples can be more easily obtained, and the turnaround time can be shorter (now as little as ten days). As a field—across academic, industry and other partners in oncology—we know this optimization needs to happen for patients, and many stakeholders are making an effort in this area.
The other area we’ve seen progress is in the understanding of co-mutations. If a gene is truly at the source of the cancer, we call that the “driver oncogene.” In most cases for newly diagnosed patients, the tumor will only have one driver oncogene, such asEGFRmutation. However, other co-occurring genomic alterations, or co-mutations, are also biomarkers and impact response and long-term outcomes for patients. We may not have the answers yet as to how to best serve some of these populations—but by discovering the problem first, we can move forward with research. And one day, this may inform new therapies as well.
How do we see NGS used in clinical practice today? Is this something that most patients diagnosed with cancers such as lung have access to?
I’m fortunate to have all of the testing resources available right within our center for shorter turnaround times. For newly diagnosed non-small cell lung cancers, I routinely do a panel of immunotherapy markers in the tumor and simultaneously perform NGS in the tumor or in the blood. Based on this information, I can identify the most appropriate treatment approach. The uncertainty and waiting time of those first two weeks while testing is coming in can be difficult for patients and family. I explain the response rate and duration of response may be better if we guide potential treatment based on deeper understanding of the tumor.
There has been progress with being able to offer more treatment options. This is good for patient care, but it does not negate the need for genetic testing options. More progress needs to be made to ensure NGS is being performed, and more widely available. The more we understand a given patient’s tumor, the more options we have.
Raising physician awareness of NGS is important, but also awareness for patients. Patients should be empowered to ask their doctor, “did you do the gene testing for my tumor, and what are the results?”
What progress has there been in the types of testing, and gathering of samples, in recent years?
Both tissue-based testing and blood-based biopsy, also known as liquid biopsy testing, have a role in clinical practice. For patients who have greater tumor burdens, liquid biopsy with a simple blood draw often works well. For tumor burdens where the tumor is shedding less DNA into the blood, tissue samples may be best. Each approach has pros and cons, but the key is to test.
Additionally, the field is also using biomarkers to identify and better understand co-ocurring genetic mutations and what their contribution is to treatment response or long-term outcomes. There is a growing body of work, including mine and the work of many others, showing that having new mutations at disease progression can render tumor resistance. This could potentially lead to development of novel therapeutic options.
How does liquid biopsy play a role in biomarker analysis? What are some active areas of research for liquid biopsy?
Liquid biopsy has matured in detection and logistics, such that this form of testing is a more accessible, less invasive diagnostic tool for patients and providers in clinical practice. Beyond being convenient and safe in the clinic, liquid biopsy also represents an active research area. With the ability to more easily and frequently test tumor response over time, we have learned that we can also detect methylation changes of tumors and characterize other tumor features using liquid biopsy.
There is a lot more we can continue to learn that can impact patient care and further research.
Dr. Le discloses compensated advisory services to EMD Serono, as well as consultant and advisory fees from Eli Lilly, AstraZeneca, and research funds from Eli Lilly, Boehringer Ingelheim, and Spectrum Pharmaceuticals.
1Paez, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.
2Lynch, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.