Paul Cairns, PhD
Office Phone: 215-728-5635
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. 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.Description of research projects
- Banumathy G, Cairns P. Signaling pathways in renal cell carcinoma. Cancer Biol Ther. 2010 Oct 4;10(7). [Epub ahead of print]. PubMed
- Ibragimova I, Ibáñez de Cáceres I, Hoffman AM, Potapova A, Dulaimi E, Al-Saleem T, Hudes GR, Ochs MF, Cairns P. Global reactivation of epigenetically silenced genes in prostate cancer. Cancer Prev Res (Phila). 2010 Sep;3(9):1084-92. PubMed
- Diamandis EP, Sidransky D, Laird PW, Cairns P, Bapat B. Epigenomics-based diagnostics. Clin Chem. 2010 Aug;56(8):1216-9. PubMed
- Cairns P. 5'-azacytidine expression arrays. Methods Mol Biol. 2009;507:165-74. PubMed
- Brooks, J. Cairns, P., Zeleniuch-Jacquotte, A. Promoter methylation and the detection of breast cancer. Cancer Causes Control. 2009 Nov;20(9):1539-50. PubMed
- Potapova A, Hoffman AM, Godwin AK, Al-Saleem T, Cairns P. Promoter hypermethylation of the PALB2 susceptibility gene in inherited and sporadic breast and ovarian cancer. Cancer Res. 2008 Feb 15;68(4):998-1002. PubMed
- Cairns P. Gene methylation and early detection of genitourinary cancer: the road ahead. Nat Rev Cancer. 2007 Jul;7(7):531-43. PubMed