Genetic alterations are very promising markers for molecular diagnosis and prognosis because they can precede obvious cancer and are highly specific. They can also be detected by PCR, a technique for generating large quantities of DNA from small amounts of a DNA sample, and can potentially provide diagnostic and prognostic information simultaneously. In his project, Dr. Cairns plans to examine the feasibility of molecular detection of ovarian cancer in two bodily fluids, peritoneal fluid and serum, which can contain cancer cell DNA. The main drawback of using peritoneal fluid for molecular diagnosis in high-risk women (familial ovarian cancer) is that it can only be obtained by a semi-invasive procedure. Serum, however, contains cancer cell DNA and is readily accessible in all individuals from a peripheral blood sample. Dr. Cairns will use two promising DNA-based detection approaches, through which primary ovarian tumors will be screened for these cancer-specific genetic alterations. A finding of the identical alteration in the matching peritoneal fluid and serum will indicate the presence of neoplastic cell DNA in the bodily fluid. Results may lead to a new non-invasive test for ovarian cancer and improve how and when women are diagnosed with the disease.
This project was made possible by a generous grant from the Entertainment Industry Foundation/Revlon Run/Walk for Women Los Angeles.
- Postdoctoral Fellowship with Dr. David Sidransky, Johns Hopkins Hospital, Baltimore
- PhD, Clinical Cancer Genetics, University of Birmingham, UK
- Epigenomics for the Stratification of the Aggressive Potential of Small Renal Masses and RCC.
- Ultra-Deep Sequencing of p53 Mutation in Blood for Early Detection of Curable Ovarian Cancer.
- Characterization and Biology of a Novel Molecular Subgroup of HGS Ovarian Cancer.
- Methylation and Sequence Mutation for Prediction of Risk of Breast Cancer in Women with Benign Disease or DCIS.
- Identification of an Epigenetic Signature for Progression in Superficial Urothelial Cancer.
The field of epigenetics addresses the set of stable changes that influence gene expression patterns that do not arise from primary mutations in gene sequence. The primary focus of our research program is the translation of basic knowledge of the epigenetics of cancer to improve the early detection, prognosis, and prediction of response to treatment of cancer through novel and well-conceived molecular tests.
Cancer is a disease initiated and driven by the accumulation of genetic and epigenetic alterations of key genes acquired over a lifetime. These alterations can be used as targets for the detection of tumor cells in clinical specimens such as needle biopsies, or body fluids such as blood or urine i.e. liquid biopsies. A molecular test that targets gene alterations at the DNA level has several conceptual advantages for the successful early detection of cancer. The alteration may be present, and therefore potentially detectable, before the cancer can be found by imaging or traditional pathology. This is because either the alteration precedes overt cancer growth, or the abnormal cells represent a tiny fraction of the cell population in the biopsy. We pioneered methylation-based early detection of prostate, kidney and bladder cancer in urine, as well as ovarian and breast cancer in blood, and we are at the forefront of developing metrics for the more rapid and robust validation of molecular tests.
It is well known that patients with the same type and stage of cancer can have different outcomes. We are developing an aggressiveness index to predict how likely it is that a tumor will recur and progress or not, based on the epigenetic heterogeneity that underlies the different behavior of each person’s tumor. The ultimate goal is to simultaneously detect a cancer at an early curable stage, and to predict the best management based on the potential of the cancer to progress.
As we uncover the genes that are altered in cancer, we are investigating if epigenetic silencing of genes with a strong biological rationale can be used to predict a better or worse response to particular therapies. At present, we cannot predict whom a specific type of chemotherapy will work for. If we could identify, ahead of time, the people who will show a poor response, oncologists could give additional or different treatment. Epigenetic alterations are potentially reversible by treatment with certain drugs; hence, it may be possible to restore the sensitivity of a tumor to a standard chemotherapy.