OMF Funded Research
Investing in promising cancer research is the primary path to “See a Cure” and since its founding in 2003, OMF has raised almost two million dollars for OM research.
Since 2013, OMF has partnered with the American Association of Cancer Research (AACR) to provide tailored research grants such as Career Development Awards and annual, peer-reviewed research awards to postdoctoral or clinical research fellows who are conducting ocular melanoma research.
These grants not only provide funding for ocular melanoma research, they also encourage both promising and established researchers to establish and continue successful careers in ophthalmology, ocular oncology, melanoma biology, or a similar field.
Since 2013, OMF has partnered with the American Association of Cancer Research (AACR) to provide tailored research grants such as Career Development Awards and annual, peer-reviewed research awards to postdoctoral or clinical research fellows who are conducting ocular melanoma research.
These grants not only provide funding for ocular melanoma research, they also encourage both promising and established researchers to establish and continue successful careers in ophthalmology, ocular oncology, melanoma biology, or a similar field.
2022 AACR-OMF Career Development Award
$150,000
Research Overview
Uveal melanoma is a rare melanoma subtype associated with poor outcomes in the metastatic setting. Virtually all cases harbor activating mutations of GNAQ, GNA11, PLCB4 or CYSLTR2 which result in activation of the MAP kinase pathway, amongst others. In addition, epigenetic dysregulation is known to play a critical role in disease pathogenesis. Based on preclinical data showing that the combination of MEK inhibition and Bromodomain and Extra-terminal (BET) protein inhibition (an epigenetic regulator) is associated with synergistic anti-tumor activity, Dr. Khan will investigate the safety and efficacy of combined BET and MEK inhibition in a multi-center phase I/II clinical trial in patients with metastatic uveal melanoma. Translational components of this study will assess potential mechanisms of treatment response and resistance using tumor and blood samples from patients.
Biography
Dr. Khan is an Assistant Professor of Medicine at the Columbia University Herbert Irving Comprehensive Cancer Center. He received his medical degree from the New York College of Osteopathic Medicine after which he completed his training in internal medicine at Medstar Georgetown University Hospital and hematology and medical oncology at Columbia University Medical Center. Dr. Khan’s research is focused on the development of novel therapies for the treatment of cutaneous malignancies, including cutaneous squamous cell carcinoma and uveal melanoma.
Acknowledgment of Support
It is a tremendous honor to be the recipient of the 2022 AACR-Ocular Melanoma Foundation Career Development Award, in honor of Robert C. Allen, MD. This award will be critical as I develop my research career and will be an important resource to facilitate the conduct and analysis of this promising clinical trial.
Uveal melanoma is a rare melanoma subtype associated with poor outcomes in the metastatic setting. Virtually all cases harbor activating mutations of GNAQ, GNA11, PLCB4 or CYSLTR2 which result in activation of the MAP kinase pathway, amongst others. In addition, epigenetic dysregulation is known to play a critical role in disease pathogenesis. Based on preclinical data showing that the combination of MEK inhibition and Bromodomain and Extra-terminal (BET) protein inhibition (an epigenetic regulator) is associated with synergistic anti-tumor activity, Dr. Khan will investigate the safety and efficacy of combined BET and MEK inhibition in a multi-center phase I/II clinical trial in patients with metastatic uveal melanoma. Translational components of this study will assess potential mechanisms of treatment response and resistance using tumor and blood samples from patients.
Biography
Dr. Khan is an Assistant Professor of Medicine at the Columbia University Herbert Irving Comprehensive Cancer Center. He received his medical degree from the New York College of Osteopathic Medicine after which he completed his training in internal medicine at Medstar Georgetown University Hospital and hematology and medical oncology at Columbia University Medical Center. Dr. Khan’s research is focused on the development of novel therapies for the treatment of cutaneous malignancies, including cutaneous squamous cell carcinoma and uveal melanoma.
Acknowledgment of Support
It is a tremendous honor to be the recipient of the 2022 AACR-Ocular Melanoma Foundation Career Development Award, in honor of Robert C. Allen, MD. This award will be critical as I develop my research career and will be an important resource to facilitate the conduct and analysis of this promising clinical trial.
2021 AACR-OMF Career Development Award
$150,000
Research Overview
Due to the failure of current treatment regimens to significantly prolong the survival of patients with uveal melanoma metastases, it is of outmost importance to develop new treatments for this patient group. Dr. Bagge is set to conduct a Phase I clinical trial on the combination of isolated hepatic perfusion with melphalan and the immune checkpoint inhibitors ipilimumab and nivolumab in uveal melanoma patients with liver metastasis. To further delineate the immunological effects of the combined treatment he plans to conduct advanced FACS and genomic analyses of tumour and blood samples from enrolled patients.
Biography
Dr. Bagge is a senior consultant surgeon at Sahlgrenska University Hospital and an associate professor at the University of Gothenburg, Sweden. He is responsible for isolated hyperthermic perfusion in Sweden and treats all patients requiring either isolated limb perfusion or isolated hepatic perfusion. Dr. Bagge is also a research group leader at the Wallenberg Center for Molecular and Translational Medicine. He conducts both clinical and preclinical research, with a special focus on treatments for both cutaneous and ocular melanoma.
Acknowledgment of Support
I am truly honored and grateful to be the recipient of the 2021 AACR-Ocular Melanoma Foundation Career Development Award, in honor of Robert C. Allen, MD. This recognition is extremely important in our joint quest to address the unmet need for effective treatments for patients with metastatic ocular melanoma.
Due to the failure of current treatment regimens to significantly prolong the survival of patients with uveal melanoma metastases, it is of outmost importance to develop new treatments for this patient group. Dr. Bagge is set to conduct a Phase I clinical trial on the combination of isolated hepatic perfusion with melphalan and the immune checkpoint inhibitors ipilimumab and nivolumab in uveal melanoma patients with liver metastasis. To further delineate the immunological effects of the combined treatment he plans to conduct advanced FACS and genomic analyses of tumour and blood samples from enrolled patients.
Biography
Dr. Bagge is a senior consultant surgeon at Sahlgrenska University Hospital and an associate professor at the University of Gothenburg, Sweden. He is responsible for isolated hyperthermic perfusion in Sweden and treats all patients requiring either isolated limb perfusion or isolated hepatic perfusion. Dr. Bagge is also a research group leader at the Wallenberg Center for Molecular and Translational Medicine. He conducts both clinical and preclinical research, with a special focus on treatments for both cutaneous and ocular melanoma.
Acknowledgment of Support
I am truly honored and grateful to be the recipient of the 2021 AACR-Ocular Melanoma Foundation Career Development Award, in honor of Robert C. Allen, MD. This recognition is extremely important in our joint quest to address the unmet need for effective treatments for patients with metastatic ocular melanoma.
2020 AACR-Ocular Melanoma Foundation Fellowship
$50,000
Awarded to: Anna Han, PhD, Thomas Jefferson University
Research Overview
Dr. Han's research proposal includes two aims: (1) to define unique metabolic features of UM that can be targetable, and (2) to identify metabolic functions of BAP1 mutations in UM. Dr. Han will study the possible roles of GNAQ/GNA11 mutations along with other frequently dysregulated oncogenic signaling pathways such as the PI3K/Akt/mTOR pathway, in upregulating lipogenesis in UM, and also compare BAP1-deficient and BAP1 re-expressed UM cell lines previously generated, eliminating confounding factors due to cell type differences.
Read more including the full abstract here.
Biography
Anna Han is a Post Doctoral Fellow at Thomas Jefferson University and a member of the Uveal Melanoma Working Group. Anna studies the therapeutic options that target metabolism in uveal melanoma and in subtypes of BAP1-deficient uveal melanoma.
Research Overview
Dr. Han's research proposal includes two aims: (1) to define unique metabolic features of UM that can be targetable, and (2) to identify metabolic functions of BAP1 mutations in UM. Dr. Han will study the possible roles of GNAQ/GNA11 mutations along with other frequently dysregulated oncogenic signaling pathways such as the PI3K/Akt/mTOR pathway, in upregulating lipogenesis in UM, and also compare BAP1-deficient and BAP1 re-expressed UM cell lines previously generated, eliminating confounding factors due to cell type differences.
Read more including the full abstract here.
Biography
Anna Han is a Post Doctoral Fellow at Thomas Jefferson University and a member of the Uveal Melanoma Working Group. Anna studies the therapeutic options that target metabolism in uveal melanoma and in subtypes of BAP1-deficient uveal melanoma.
2018 AACR-OMF Career Development Award
$150,000
Research Overview
Uveal melanoma is an aggressive intraocular cancer associated with high rates of metastatic disease. Although highly predictive molecular prognostic testing for uveal melanoma is available, it requires tumor tissue that is not always accessible via tumor biopsy. Dr. Skalet’s group has identified circulating cells in patients with uveal melanoma that are hybrids of macrophage and tumor cells. She is set to determine the prognostic power of these circulating hybrid cells in uveal melanoma patients undergoing primary treatment and to correlate the levels of these cells with clinical staging and gene expression profile classification.
Biography
Dr. Skalet completed her MD/PhD at the University of Pennsylvania. Following an internship at Children’s Hospital of Philadelphia, she completed her ophthalmology residency at the University of California, San Francisco, and subspecialty training in ocular oncology and ophthalmic pathology at Oregon Health and Science University (OHSU). She is currently an assistant professor of ophthalmology at the Casey Eye Institute, OHSU. Her research focuses on early detection of uveal melanoma and vision-threatening complications of radiation treatment.
Acknowledgement of Support
This grant award supports exploration of a novel circulating tumor cell population as a non-invasive prognostic biomarker and source for genetic information in uveal melanoma. Development of this novel biomarker permits pursuit of a line of inquiry with potential to open a new conceptual area in uveal melanoma research.
Uveal melanoma is an aggressive intraocular cancer associated with high rates of metastatic disease. Although highly predictive molecular prognostic testing for uveal melanoma is available, it requires tumor tissue that is not always accessible via tumor biopsy. Dr. Skalet’s group has identified circulating cells in patients with uveal melanoma that are hybrids of macrophage and tumor cells. She is set to determine the prognostic power of these circulating hybrid cells in uveal melanoma patients undergoing primary treatment and to correlate the levels of these cells with clinical staging and gene expression profile classification.
Biography
Dr. Skalet completed her MD/PhD at the University of Pennsylvania. Following an internship at Children’s Hospital of Philadelphia, she completed her ophthalmology residency at the University of California, San Francisco, and subspecialty training in ocular oncology and ophthalmic pathology at Oregon Health and Science University (OHSU). She is currently an assistant professor of ophthalmology at the Casey Eye Institute, OHSU. Her research focuses on early detection of uveal melanoma and vision-threatening complications of radiation treatment.
Acknowledgement of Support
This grant award supports exploration of a novel circulating tumor cell population as a non-invasive prognostic biomarker and source for genetic information in uveal melanoma. Development of this novel biomarker permits pursuit of a line of inquiry with potential to open a new conceptual area in uveal melanoma research.
2017 AACR-OMF/Kammerman Family Fellowship
$50,000
Awarded to: Vivian Chua, PhD, Sidney Kimmel Cancer Center, Thomas Jefferson University (Philadelphia, PA)
Title: Novel Epigenetic Targeting Approaches in Uveal Melanoma (UM)
Dr. Chua's reseach focuses on how bromodomain protein inhibitors can effectively reduce metastatic UM cell growth. A second aim of the research is to investigate whether cells in the liver microenvironment would produce factors/proteins that may alter the responses of UM tumor cells to bromodomain inhibitors.
Title: Novel Epigenetic Targeting Approaches in Uveal Melanoma (UM)
Dr. Chua's reseach focuses on how bromodomain protein inhibitors can effectively reduce metastatic UM cell growth. A second aim of the research is to investigate whether cells in the liver microenvironment would produce factors/proteins that may alter the responses of UM tumor cells to bromodomain inhibitors.
2016 AACR-Ocular Melanoma Foundation Fellowship
$50,000
Jessica Teh, PhD, Sidney Kimmel Cancer Center, Thomas Jefferson University (Philadelphia, PA)
Title: Utility of CDK4/6 Inhibitors in Uveal Melanoma
After treatment of primary uveal melanoma tumors, 50% of patients will develop macro-metastases and currently there are no FDA-approved targeted inhibitor treatments for metastatic UM. MEK-ERK1/2 signaling is activated frequently in uveal melanoma due to driver mutations in either GNAQ or GNA11. While MEK inhibitors are FDA-approved in cutaneous melanoma, they provide a 14% response rate and modestly improve progression-free survival in uveal melanoma. Dr. Teh’s proposal aims to utilize an in vivo reporter model to monitor the effects of the combination of MEK and CDK4/6 inhibitors and to identify optimal dosing schemes for this combination. Additionally, she will work on determining the effect of BAP1 status in the modulation of response to the combination leveraging new metastatic uveal melanoma cell lines, a new in vivo metastatic colonization model, and uveal melanoma patient samples from clinical trials. Dr. Teh hopes to ultimately provide the pre-clinical basis for targeted inhibitor combinations in late-stage uveal melanoma.
Title: Utility of CDK4/6 Inhibitors in Uveal Melanoma
After treatment of primary uveal melanoma tumors, 50% of patients will develop macro-metastases and currently there are no FDA-approved targeted inhibitor treatments for metastatic UM. MEK-ERK1/2 signaling is activated frequently in uveal melanoma due to driver mutations in either GNAQ or GNA11. While MEK inhibitors are FDA-approved in cutaneous melanoma, they provide a 14% response rate and modestly improve progression-free survival in uveal melanoma. Dr. Teh’s proposal aims to utilize an in vivo reporter model to monitor the effects of the combination of MEK and CDK4/6 inhibitors and to identify optimal dosing schemes for this combination. Additionally, she will work on determining the effect of BAP1 status in the modulation of response to the combination leveraging new metastatic uveal melanoma cell lines, a new in vivo metastatic colonization model, and uveal melanoma patient samples from clinical trials. Dr. Teh hopes to ultimately provide the pre-clinical basis for targeted inhibitor combinations in late-stage uveal melanoma.
2015 AACR-Ocular Melanoma Foundation Fellowship
$50,000
Stefan Kurtenbach, MD, Miller School of Medicine of the University of Miami (Miami, FL)
Title: BAP1 Loss Deregulates Neural Crest Guidance Cue Signaling in Uveal Melanoma
Findings: Although Dr. Kurtenbach’s research is ongoing, initial results found PRAME mRNA as the most significant predictor for metastasis in Class 1 tumors. These results have been published in “Clinical Cancer Research” (http://clincancerres.aacrjournals.org/content/22/5/1234).
Title: BAP1 Loss Deregulates Neural Crest Guidance Cue Signaling in Uveal Melanoma
Findings: Although Dr. Kurtenbach’s research is ongoing, initial results found PRAME mRNA as the most significant predictor for metastasis in Class 1 tumors. These results have been published in “Clinical Cancer Research” (http://clincancerres.aacrjournals.org/content/22/5/1234).
2014 AACR-Ocular Melanoma Foundation Fellowship
$50,000
Alexander Shoushtari, MD, Sloan-Kettering Institute for Cancer Research (New York, NY)
Title: Overcoming Resistance to MEK Inhibition in Advanced Uveal Melanoma
Synopsis: Dr. Shoushtari helped coordinate a randomized, multicenter trial combining a MEK inhibitor called trametinib with/without an AKT inhibitor called GSK2141795. This represented a novel approach to treating ocular melanoma and tested the scientific hypothesis that combined MEK and AKT inhibition is better than MEK inhibition alone.
As part of the clinical trial, tumor biopsies were taken before and during treatment. Dr. Shoushtari and colleagues analyzed the genetic changes during treatment in the biopsy specimens and compared patients whose tumors responded to therapy with those whose tumors did not respond to therapy. Comparing these tumors will help shed light on how uveal melanomas rely on MAPK, AKT, or other growth signaling pathways to grow. The results of the research are being applied to help plan new approaches to treating uveal melanoma, and will be generalizable to other types of tumors that rely on these growth pathways.
Findings: Two benefits of the study were the amassing of the largest annotated biorepository of uveal melanoma and cultivating the research across multiple centers in the United States and Europe. In Shoushtari’s words, “The fact that we were able to accrue rapidly across multiple centers shows unequivocally that multicenter trials in this rare disease can be conducted efficiently.”
Title: Overcoming Resistance to MEK Inhibition in Advanced Uveal Melanoma
Synopsis: Dr. Shoushtari helped coordinate a randomized, multicenter trial combining a MEK inhibitor called trametinib with/without an AKT inhibitor called GSK2141795. This represented a novel approach to treating ocular melanoma and tested the scientific hypothesis that combined MEK and AKT inhibition is better than MEK inhibition alone.
As part of the clinical trial, tumor biopsies were taken before and during treatment. Dr. Shoushtari and colleagues analyzed the genetic changes during treatment in the biopsy specimens and compared patients whose tumors responded to therapy with those whose tumors did not respond to therapy. Comparing these tumors will help shed light on how uveal melanomas rely on MAPK, AKT, or other growth signaling pathways to grow. The results of the research are being applied to help plan new approaches to treating uveal melanoma, and will be generalizable to other types of tumors that rely on these growth pathways.
Findings: Two benefits of the study were the amassing of the largest annotated biorepository of uveal melanoma and cultivating the research across multiple centers in the United States and Europe. In Shoushtari’s words, “The fact that we were able to accrue rapidly across multiple centers shows unequivocally that multicenter trials in this rare disease can be conducted efficiently.”
