Lab In The News
Melanoma Researchers Gathered at Wistar to Assess How Far We’ve Come and How Far We Still Need to Go
In a time when targeted therapies and immunotherapies have revolutionized the treatment options for melanoma patients, and yet a substantial proportion of them don’t benefit from these new approaches, researchers are looking for factors that affect the host response and how to modulate them.
Older Melanoma Patients Have Better Response to Immune Checkpoint Blockade Therapy
Patient age correlates with response to immunotherapy in melanoma and depleting regulatory T cells in young patients may have a therapeutic potential to enhance response in younger patients, according to research from The Wistar Institute.
The Weeraratna Laboratory
The primary focus of the Weeraratna laboratory is the study of how melanoma spreads, or metastasizes. The progression of melanoma from early to late stage involves a series of signaling changes within the cell, often described in terms of “pathways.” In particular, the lab studies the non-canonical Wnt signaling pathway, which comprises a family of proteins with great implications in fetal development as well as cancer. Changes in genes and their protein products involved in this pathway affect how malignant cells multiply, move throughout the body, and invade other tissues.
Another major interest of the laboratory lies in exploring how changes in the microenvironment, or the cellular environment in which the tumor exists, including immune cells, fibroblasts, blood vessels, and signaling molecules, contribute to both tumor progression and therapy resistance. These changes may be induced by external factors, such as chemotherapy or irradiation, or naturally occurring phenomena, such as hypoxia and aging. Melanoma incidence is increased in elderly patients, who also have a worse prognosis, and this could be due to a number of age-related factors, such as a lower immunity, but may also be due to changes in the aging microenvironment. Using melanoma cells and both young and old normal skin cells as a model, the lab is trying to unravel what these changes may be, and how they affect tumor progression.
Marie Webster, Ph.D.
Filipe Almeida, Ph.D.
Stephen Douglass, Ph.D.
Mitchell Fane, Ph.D.
Kugel, C.H., Douglass, S.M., Weeraratna, A.T., et al. (in press) "Age-related differences in intra-tumoral Tregs dictate response to anti-PD1." Clinical Cancer Research
Behera, R., Kaur, A., Weeraratna, A.T., et al. "Inhibition of Age-Related Therapy Resistance in Melanoma by Rosiglitazone-Mediated Induction of Klotho." Clin Cancer Res. 2017 Jun 15;23(12):3181-3190. doi: 10.1158/1078-0432.CCR-17-0201. Epub 2017 Feb 23.
Kaur, A., Webster, M.R., Weeraratna, A.T., et al. "sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance." Nature. 2016 Apr 14;532(7598):250-4. doi: 10.1038/nature17392. Epub 2016 Apr 4.
Webster, M,R., Xu, M., Kinzler, K.A., Weeraratna, A.T., et al. "Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells." Pigment Cell Melanoma Res. 2015 Mar;28(2):184-95. doi: 10.1111/pcmr.12330. Epub 2014 Dec 29.
O'Connell, M.P., Marchbank, K., Weeraratna, A.T., et al. "Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2." Cancer Discov. 2013 Dec;3(12):1378-93. doi: 10.1158/2159-8290.CD-13-0005. Epub 2013 Oct 8.
Jessie Villanueva, Ph.D.
Associate Professor, Molecular & Cellular Oncogenesis Program
Member, The Wistar Institute Melanoma Research Center