Biomarker Discovery Program
Biomarkers are molecular substances in the body that can be used to indicate health or disease. These biomarkers can be found in blood, urine, other body fluids and tissue. Prostate cancer is just one example of where the use of biomarkers can lead to individualized diagnosis and treatment.
While prostate cancer is the most commonly diagnosed cancer among U.S. men, most of these cancers are not aggressive. Nearly half of all men diagnosed with prostate cancer have insignificant disease that does not require any treatment.
But today, identifying these men is challenging. When examining a sample of a patient's prostate tissue from a needle biopsy specimen, the pathologist has to rely on physical or pathologic characteristics to determine whether the tumor is aggressive. Unfortunately, in many instances, the pathologist cannot separate insignificant from aggressive cancer. Biomarkers can help the pathologist make this separation possible.
The Biomarker Discovery Program aims to solve clinical dilemmas like this across a spectrum of diseases. For prostate cancer, if we can find molecular biomarkers that predict the course of each patient's disease, we could reduce overtreatment of more than 50,000 U.S. men a year while also minimizing undertreatment, overdiagnosis and underdiagnosis.
Using multidisciplinary teams, the Biomarker Discovery Program takes a clinical question and answers it through a four-phase approach: discovery, experimental validation, preclinical validation and clinical validation.
This project's goal is to use biomarkers to better stratify men with prostate cancer and individualize their treatment. This includes separating insignificant prostate cancer from significant prostate cancer on needle biopsy specimens and identifying particularly aggressive prostate cancer in men undergoing surgery.
To accomplish this, we are performing genetic profiling of insignificant, significant and aggressive prostate cancer using whole-genome sequencing technologies to discover DNA alterations that characterize an individual tumor and provide information on tumor behavior.
This projects aims to assess the level of surgery required for a patient undergoing treatment for endometrial cancer. Endometrial cancer first spreads to lymph nodes surrounding the uterus, so during surgery, it is important to remove the uterus and the regional lymph nodes — a procedure called a lymphadenectomy — so that all the cancer is removed and the patient is treated appropriately.
However, in most patients undergoing surgery, the tumor has not spread beyond the uterus, which means a lymphadenectomy is unnecessary. Lymphadenectomy is expensive, time-consuming, and associated with complications and risks, so not performing the procedure has significant benefits to patients.
The goal of this study is to identify biomarkers that can identify patients that have a high likelihood of their cancer spreading outside the uterus to the regional lymph nodes. Lymph nodes could then be surgically resected from these patients that benefit from the surgery. Other patients who are identified as having a low risk of spread would be spared a lymphadenectomy.
Ultimately, such biomarkers will individualize treatment for each patient while saving time and reducing risks, complications and expense due to unnecessary surgery.
Peripheral T-cell Lymphoma
Our goal is to identify biomarkers by developing an integrative genetic model of risk in peripheral T-cell lymphoma, a cancer of the immune system. Using a combination of these markers, we will be able to predict the course of disease and response to treatment.
Patients with aggressive peripheral T-cell lymphomas as determined from these biomarkers may benefit from more-intense therapies, such as stem cell transplantation. These treatments may cure patients, but they are more toxic than conventional therapy.
Biomarkers would identify patients most likely to benefit from these treatments and spare patients from toxic therapies if they would get no benefit.
Liver fibrosis occurs as a result of a number of injuries to the liver, such as viral hepatitis. When monitoring the health and function of the liver, it is important to have a measure of the amount of fibrosis, also known as stage of fibrosis.
Currently, imaging modalities such as CT scans have a very limited ability to determine the amount of fibrosis. Liver fibrosis can also be assessed by sampling the liver through a biopsy procedure, but this is an invasive technique with complications.
In this project, we are applying an imaging technique called 3-D magnetic resonance elastography to determine the amount of liver fibrosis. This technique allows for noninvasive assessment of liver elasticity to determine the stage of fibrosis. This has many benefits, including the elimination of the need for liver biopsy in patients with chronic liver disease.
In the U.S. and worldwide, lung cancer causes more deaths than any other type of cancer. Lung cancer is not a single tumor type but rather is composed of a number of different types of cancer, each with its challenges in diagnosis and predicting behavior and response to treatment.
The lung cancer group in the Biomarker Discovery Program has multiple projects targeting these different challenges, such as predicting the course of disease and identifying novel therapeutic targets in adenocarcinoma and identifying screening biomarkers in squamous cell carcinoma.
In patients who present with more than one lung tumor, we are identifying biomarkers to determine if these are two separate tumors or related tumors, which is critical when choosing appropriate treatment for patients with multiple lung tumors.
Finally, some tumors have neuroendocrine features (a form of differentiation) that can be identified with biomarkers, and we are identifying the role of these markers in predicting tumor behavior.
Each of these projects will help individual patients receive the most accurate information regarding their cancer and also receive the most appropriate treatment.