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The Society for Melanoma Research Newsletter Published By: The Society for Melanoma Research

Volume 32 | January 2020

Edited by: Gretchen M. Alicea, Ph.D. Candidate & Vito W. Rebecca, Ph.D.

Letter from the SMR President

As 2019 draws to a close, I have been reflecting upon the reasons for our success as the Society for Melanoma Research, a Society that has been going from strength to strength for the past 16 years, since its formation instigated by our first President, Meenhard Herlyn. Here are my thoughts as we welcome 2020.

SMR is built on sheer passion – a passion to understand and a passion to make a difference. As a Society we cover a breadth of science; the biology and function of pigment cells, the addictive nature of UV radiation to humans, the transition from melanocyte to melanoma, the impact of the tumour microenvironment, prevention of melanoma, drug therapy response and resistance, prognosis, diagnosis, genomics, etc. This breadth reflects our membership, which includes people with a diverse set of skills and expertise. And this is our success. The results achieved in melanoma research in the last two decades have impacted so many areas of science, and indeed many other cancers, and our success is due to our multi-disciplinary approach, inclusiveness, collaborative spirit, and single shared goal to “alleviate the suffering of people with melanoma”. We are a small but nimble and strong group, and by keeping our eye on our goal, we will continue to achieve amazing things together.

The SMR community shares knowledge and experience annually, and 2019 saw another excellent Annual Congress (the 16th Annual Congress) in Salt Lake City. Presentations from the congress are highlighted in this newsletter, and I would like to thank the organising committee (chaired by Martin McMahon and Sheri Holmen) for putting together a wonderful program that included basic science, translational research and clinical medicine. The congress is central to our activities as a Society, not only to share knowledge, but it is also an opportunity to enhance our collaborations and provide the infrastructure and support for important endeavours. For example in 2019: The AJCC melanoma/skin cancer sub-committee met to discuss the next set of analyses to further refine prognosis at melanoma diagnosis; a group was formed to put together a White Paper on the clinical use of prognostic tissue-based tests for early melanoma; and the Melanoma Research Foundation held another workshop on “The State of Melanoma: Challenges and Opportunities”.

Another important aspect of SMR is recognizing and celebrating our successes. Each year at the congress, awards are bestowed on those who have made important contributions to the field, and for 2019 the following people were duly recognized; Keith Flaherty (Lifetime Achievement), Chris Marine (Outstanding Research), Sheri Holmen (Estela Medrano Award), David Olmeda (Christopher J Marshall Award), Carmit Levy (Young Investigator). Congratulations to all awardees, and to the many travel awardees (our rising stars we support to attend the congress). Nominations for the awards are open and can be made via https://www.societymelanomaresearch.org/awards.

I also have the pleasure of welcoming the new editorial team for our newsletter - Rohit Thakur, Rebecca Lee, Karla Lee, Vito Rebecca, Jarem Edwards, Gretchen Alicea, Claire Hardie, Daniela Cerezo Wallis. I thank them and the advisors, Ashani Weeraratna and Marie Webster, for volunteering their time.

Importantly, I would also like to thank the executive committee, including Keith Flaherty (Past-President), Ashani Weeraratna (President-Elect), Michael Davies (Secretary) and Anja Bosserhoff (our long-serving Treasurer) for their support and leadership, the steering committee members for their contribution to our organisation, and Site Solutions for the administrative support.

On behalf of the executive committee we wish you a safe and successful 2020, and together we will continue to “alleviate the suffering of people with melanoma” through our research!

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Melanoma News

This year’s SMR congress was held in beautiful Salt Lake, Utah. We were welcomed to the congress by our SMR President, Georgina V Long, who called for increased melanoma awareness, prevention and early diagnosis, with the slogan “Game on Mole”. Professor Thea Tisty from the University of California gave the keynote presentation that emphasized the importance of the tumor microenvironment on breast cancer risk and progression, which parallels themes many in our melanoma community reported during the congress. Her laboratory identified an association between high mammographic density and desmoplastic tumor tissue that correlates with repression of the fatty acid transporter CD36. This presentation was followed by an excellent welcome reception.

Women in Science Session at the SMR

Written By: Gretchen M. Alicea and Vito W. Rebecca

This year’s Women in Science session marked the 12th anniversary of this critical event and was nothing short of spectacular. This session was started in 2008 by Ashani Weeraratna with the overall goal to discuss issues presently impacting woman and minorities in science and, importantly, considering what we can do to solve them. This year’s session was organized by Jennifer McQuade, Allison Betof Warner and Marie Webster. The session was open to everyone, not only female scientists, and was excellently attended by trainees, young investigators and leaders in the field. An illuminating presentation was given by Mary C. Beckerle, CEO of the Huntsman Cancer Institute, whose words brought much needed attention to the reality that while women comprise roughly 50% of the graduate student pool, female representation decreases significantly in leadership positions. Women represent only 22% of full professors, 16% of department chairs and deans, and 13% of cancer center directors. Additionally, 50% of mothers leave academia after their first child. In terms of grants, women in high-ranking science positions receive fewer total research grants and lower research dollars relative to men.

In regard to the demographic landscape of all female doctorate graduates in the fields of science and engineering, 86% are White or Asian, fewer than 4% are Latinas, and less than 3% are Black. The same can be observed in the job market, with only 1 out of 20 employed scientists and engineers being Black women or Latinas. These numbers demonstrate that gender and racial gaps in the sciences continue to be an issue in 2020 and we have to do more to address it. Dr. Beckerle left us with words of advice for achieving professional joy.

We should all try to:

  • Have a commitment to service; something greater than yourself
  • Have a frontier spirit
  • Have a pinch of resilience and leap of optimism
  • Integrate the professional and the personal
  • Keep the threads on your tires
  • Do your best and let that be enough

Later on, the attendees were given 10 discussion topics to select from and form small groups. The topics that were discussed and topic moderators were:

In summary, the Women in Science was a complete success. This has become a favorite session that we all look forward to every year. We all left with ideas on how to do and be better. We thank everyone that attended this session and all the moderators.

All the best to you all and Happy New Year!

Gretchen and Vito

Below, find some exceptional Twitter hashtags along these same veins.

Highlights from the 2019 SMR Meeting

By President Georgina V. Long, Michael A. Davies, Gretchen M. Alicea and Vito W. Rebecca

The highlight from this year’s congress was that we all came together to share ideas. Importantly, many collaborations and think-tanks were born from the meeting.

In terms of basic science, sessions focused on RAS Family GTPase Signaling, Signaling Pathways and Targeted Therapies, Melanoma Epigenetics, Metabolism and Melanoma, and the Immune System were superb, with presentations illuminating what gaps still remain in our understanding of how to effectively cure melanoma despite the great progress that has been made. ‘Modeling Melanoma in the Immunotherapy Era’ and ‘Melanoma Metastasis: Models and Mechanism’ sessions updated to current and emerging experimentally model systems to help investigators to address many of the key challenges melanoma patients now face. ‘Advances in Acral, Mucosal and Uveal Melanoma’ provided an excellent venue for focused investigations for these understudied subtypes of melanoma, with potential efficacious therapy strategies on the horizon for these patients. Below are only a few of the first-class presentations given at the meeting:

  1. In the Microenvironment session, we heard work from Dr. Mitchell Fane that builds on observations from the Weeraratna lab showing differences in response to therapy in aged versus younger patients. Dr. Fane presented exemplary work identifying how differentially secreted factors in aged versus young lung fibroblasts have dramatic consequences on tumor dormancy phenotypes, metastatic dissemination and anti-tumor immune responses.
  2. In the Melanoma Metastasis: Models and Mechanism session, Dr. Nathaniel Campbell from the Xavier lab presented excellent work supporting the hypothesis that distinct clusters of either invasive (AXL+) or proliferative (MITF+) cells cooperate to promote metastasis using a zebrafish model. Interestingly, these data suggest that these two cellular states (invasive or proliferative) may not be interchangeable as the phenotype switching model suggests.
  3. In the Melanoma and the Immune System session, Dr. Daniela Cerezo-Wallis presented compelling evidence for the melanoma-secreted protein MIDKINE in reprogramming melanoma cells towards an immune-suppressive secretome state that correlated with increased pro-tumoral macrophages and dysfunctional T cells. This work unravels melanoma-immune evasion mechanisms and identifies MIDKINE as a possible target to increase efficacy in immunotherapy-resistant patients.
  4. During the Microenvironment session, Dr. Samantha J. Stehbens presented fantastic high-resolution live-cell imaging of melanoma cells navigating 3D matrices following loss of the microtubule binding proteins, CLASPs. Pan-depletion of CLASPs within melanoma cells resulted in stasis and reduced viability following conditions of 3D confinement, suggesting a potential vulnerability critical in melanoma metastasis.

On the clinical side, the session on neoadjuvant therapy was excellent – a great platform for rapid drug development, and to explore resistance in patients through the collection and analysis of high-quality biospecimens. The ‘Late Breaking Clinical Abstracts’ session included updates from several key clinical trials in advanced melanoma patients. These presentations highlighted many of the key clinical questions in the field, and provided a foundation and framework for translational research;

  1. Keynote 022, a phase 2 study, showed a persistent and increasing evidence of improvement of pembrolizumab + dabrafenib + trametinib (anti-PD1+BRAF+MEK) versus dabrafenib + trametinib alone. This was particularly evident in the landmark PFS (41% vs 16%), and in the duration of responses (median 25.1 vs 12.1 months). However, this was associated with increased toxicity, and to date has not resulted in a statistically significant improvement in overall survival.
  2. Checkmate 067 demonstrated that one of the best predictors of long-term outcome is the amount of tumor shrinkage on the scan (i.e., the degree of response). Still, 20% of patients with a complete response (CR) had progressed by 5 years (whether they received nivolumab or nivolumab + ipilimumab). Investigations are ongoing to understand and predict which patients will progress after a CR, with a need for accompanying mechanistic studies. There were geographical differences in response and long-term outcomes observed as well.
  3. We saw updates from the pembrolizumab trials, including what does it mean for a patient with ‘stable disease’ in the long term, and 40% of patients with stable disease at first scan eventually have a partial or complete response.
  4. Zeynep Eroglu presented results on behalf of investigators from 17 melanoma centers around the work who retrospectively examined the outcomes with adjuvant immunotherapy in stage III melanoma patients who had not undergone a completion lymph node resection. The study addressed a data gap in our field as the use completion lymph node dissections decreased dramatically after the publication of the MSLT-II study in 2017, but this surgery was mandatory in the registration studies that led to the approval of adjuvant anti-PD-1 therapy. While additional analyses are ongoing, the initial results support that patients who receive adjuvant anti-PD-1 after a positive sentinel lymph node biopsy but without completion lymph node dissection overall appear to have good outcomes.
  5. Updates on Uveal melanoma were important as this is an area of great unmet clinical need. New data presented about the clinical trial of tebentafusp, a bispecific antibody that targets gp100 and the CD3 T-cell receptor which has shown some activity in metastatic uveal melanoma patients, identified serum levels of CXCL10 and CXCR3 + CD8+ T cells as potential early biomarkers of activity for this agent. This agent is now being evaluated in a phase III trial in uveal melanoma.

Finally, one theme running through several sessions was research on the pathogenesis and treatment of central nervous system (CNS) metastases. Dr. David Kircher, a member of Dr. Sheri Holmen’s lab, presented data implicating FAK in the development of melanoma brain metastasis in a novel mouse model. Dr. Kevin Keffman, on behalf of the lab of Dr. Eva Hernado and multiple collaborators, presented surprising data on a potential new player in brain metastasis, melanoma-secreted amyloid beta. Dr. Michael Davies showed data implicating aberrant metabolism in the formation and therapeutic resistance of melanoma brain metastases. Finally, Dr. Isabella Glitza presented a late breaking abstract describing the initial safety results from the first-ever clinical trial of intrathecal administration of anti-PD-1 in metastatic melanoma patients with leptomeningeal disease (LMD). Together these reports, along with several interesting posters, demonstrated the growing body of basic, clinical, and translational research focused on CNS metastasis in melanoma, addressing a key challenge in this disease.

SMR Member News

MRF Team Awards

Congratulations to William Sellers, MD and Keith Flaherty, MD for receiving the MRF Uveal Melanoma Team Award focused on creating a map of the immune cells in uveal melanoma to help guide future immune-oncology clinical trials for this at-risk cohort.

Congratulations to Genevieve Boland, MD, PhD, David Liu, MD, and Srinivas Saladi, PhD for receiving the MRF Cutaneous Melanoma Team Award focused on investigating the role of the Hippo pathway during melanoma immunotherapy.

MRF Established Investigator Awards

Congratulations to J. William Harbour, MD for receiving the MRF Established Investigator Award focused on illuminating the cellular and genomic landscape of uveal melanoma with single cell resolution.

Congratulations to Donald McDonnell, PhD for receiving the MRF Established Investigator Award focused on targeting the estrogen receptor to enhance melanoma immunity.

MRF Career Development Awards

Congratulations to Vito W. Rebecca, PhD for receiving the MRF Career Development Award focused on targeting melanoma developmental programs to overcome therapy resistance.

Congratulations to Stefan Kurtenbach, PhD for receiving the MRF Career Development Award focused on delineating the role of PRAME in epigenetic reprogramming and chromosomal instability in the context of uveal melanoma.

Congratulations to Venkata Saketh Sriram Dinavahi, PhD for receiving the MRF Career Development Award focused on investigating the role of p53 in melanoma brain metastases.

Congratulations to Claudia Capparelli, PhD for receiving the MRF Career Development Award focusing on understanding the role of SOX10 in WT BRAF melanoma.

Congratulations to Matthew Griffin, PhD for receiving the MRF Career Development Award focused on augmenting anti-melanoma immunotherapy efficacy by commensal microbiota.

Congratulations to Maria Sosa, PhD for receiving the MRF Career Development Award focused on therapeutically exploiting dormancy in disseminated melanoma cells.

MRF Medical Student Awards

Congratulations to Rebecca Chen, Michelle Ferreira, Hannah Knochelmann, Cory Kosche, Michael Lee, Victor Lin, Dianne Lumaquin, Alicia Mizes, Kristina Navrazhina, Kyle Tegtmeyer and Eliot Zhu for receiving the MRF Medical Student Award.

Congratulations to SMR Award Recipients!

  • Sheri Holmen, PhD - Estela Medrano Award
  • Keith Flaherty, MD - Lifetime Achievement
  • Chris Marine, PhD - Outstanding Research
  • David Olmeda, PhD - Christopher J Marshall Award
  • Carmet Levy, PhD - Young Investigator Award
Sheri Holmen, PhD - Estela Medrano Award
Keith Flaherty, PhD - Lifetime Achievement
Chris Marine, PhD - Outstanding Research
David Olmeda, PhD - Christopher J Marshall Award
Carmet Levy, PhD - Young Investigator Award

Congratulations to all of the Travel Award Recipients!

Winners Listed Alphabetically by Last Name

  • Gretchen M. Alicea
  • Yash Chhabra
  • Ana Contreras-Sandoval
  • Stephen Douglass
  • Luca Di Leo
  • Gabriela Gomez
  • Adam Guterres
  • Anna Han
  • Jaskaren Kohli
  • Daniel Lionarons
  • Ettai Markovits
  • Andrew McNeal
  • Mei Fong Ng
  • Meredith Pelster
  • Eva Perez-Guijarro
  • Shuyang Qin
  • Marika Quadri
  • Chantal Saberian
  • Jenny Mae Samson
  • Mithalesh Singh
  • Tamara Sussman
  • Rohit Thakur
  • Manoela Tiago-DosSantos
  • Megan Trager

Promotions

Congratulations to Amanda Lund, PhD on her new position at NYU Langone in 2020 where she will continue to explore the role of lymphatic vasculature in dermal and anti-tumor immunity.

Congratulations to Ashani Weeraratna, PhD on her new position as E.V. McCollum Chair of Biochemistry and Molecular Biology, Bloomberg Distinguished Professor of Cancer Biology at Johns Hopkins Bloomberg School of Public Health, and Co-Program Leader of Cancer Invasion and Metastasis at Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine.

Announcements

The SMR Newsletter Welcomes the New Editorial Team

Gretchen M. Alicea, Ph.D. Candidate: Mrs. Alicea is a graduate student at the Wistar-USciences Graduate Program. She is a member of the Weeraratna lab and co-chair of the trainee association at The Wistar Institute. Her thesis work focuses on the aging microenvironment and metabolism in melanoma. For this work she has received the Monica Shander Fellowship, a William H. Gano Fellowship and an R01 minority supplement grant. She has been selected to present her work orally in national and international conferences. Currently, she is a visiting scholar at John Hopkins Bloomberg School of Public Health and will be graduating in Spring of 2020.

Vito W. Rebecca, Ph.D.: Dr. Rebecca is a Staff Scientist from the United States working in drug development and melanoma therapy resistance. He graduated from the University of South Florida in 2014 and went on to Postdoc at the University of Pennsylvania until 2017 focusing on the development of improved lysosome inhibitors. This work culminated in first-authored 2017 and 2019 Cancer Discovery manuscripts and receipt of the 2018 Christopher J. Marshall Award. Currently, Dr. Rebecca is investigating lineage plasticity and clonal diversity in the context of therapy resistance with single cell approaches at The Wistar Institute.

Daniela Cerezo-Wallis, Ph.D.: Daniela is a postdoctoral fellow at Soengas Lab, Spanish National Cancer Research Centre (CNIO), Spain. Daniela earned a degree in Biology from the Simón Bolívar University of Venezuela in 2010, where she started her training in Oncoimmunology. Afterward, her interest in immunology led her to pursue a Master's degree at the University of Granada in Spain. During this time, Daniela worked with Dr. Jaime Sancho -from the “IPBLN” Institute- characterizing the role of the protein CD38 on the development of Rheumatoid Arthritis in animal models. After obtaining her Master’s degree, Daniela was awarded a “la Caixa” fellowship to carry her Ph.D. studies with Dr. Marisol Soengas. Daniela is now continuing her research in melanoma immunotherapy and translational medicine.

Claire M. Hardie, M.D.: Dr Hardie is a surgical trainee from the United Kingdom working in plastic surgery. She graduated from the University of Newcastle medical school in 2016 and went onto take up an academic foundation post with the Leeds Melanoma Research Group. During this post she researched the relationship between melanoma and deprivation, which was presented at the Society of Melanoma congress, 2018, and published in the Journal of Investigative Dermatology. Currently Dr Hardie is investigating imaging protocols for melanoma and surgical management of melanoma of the nail unit.

Jarem J.A Edwards, Ph.D. Candidate: Jarem is a PhD student in the laboratory of Professor Richard Scolyer and Professor Georgina Long at the Melanoma Institute of Australia (MIA). He completed his Bachelor of Science degree in 2016 at the University of Sydney, majoring in immunology and biochemistry. He then pursued an Honors of Research year with Dr. Mainthan Palendira studying the importance of CD8+ resident T cells in melanoma tumors in close collaboration with MIA. This work was published in 2018 in Clinical Cancer Research. As part of his PhD, Jarem is interested in understanding the biology of patient tumors refractive to anti-PD-1 immunotherapy and investigating alternative immune targets. Jarem also currently works as a clinical trials coordinator at MIA.

Rohit Thakur, Ph.D.: Rohit is a postdoctoral fellow at the Wargo lab, the University of Texas MD Anderson Cancer Center, Texas, US. His research focuses on understanding why some patients respond to immunotherapy and some do not using an integrative bioinformatic analysis of multi-omics data. He completed his undergraduate degree in bioinformatics in India and was awarded the prestigious Marie-Sklodowska Curie fellowship to pursue PhD degree at the University of Leeds, UK. During his PhD, he received training in statistics and melanoma tumor genetics under the supervision of Drs. Jenny Barrett, Julia Newton-Bishop and Jeremie Nsengimana.

Karla Lee, MD, PhD candidate: Karla is an Irish medical oncologist who received her MD from Trinity College Dublin in 2012. She is in training at The Royal Marsden Hospital in London and is currently in the 2nd year of a PhD examining the role of the gut microbiome in melanoma at King’s College London. Her interests are include immunology, host factors and the gut microbiota.

Rebecca Lee, MD: Dr. Lee is a clinical lecturer in medical oncology at The University of Manchester and The Christie NHS Foundation Trust and is currently is working at The Francis Crick Institute in the Sahai laboratory. Her work focuses on precision medicine approaches to melanoma treatment including circulating tumour DNA, detecting minimal residual disease and cancer cell-microenvironment interactions. She is a co-investigator on a number of translational trials examining utility of circulating tumour DNA and strategies to augment response to immune therapies.

MRF Award Announcements for 2020

Applications for the 2020 MRFBC-BMS Young Investigator Translational Immuno-Oncology Team Science Award will be accepted from January 6, 2020 until March 2, 2020 at 5pm ET. To enable young investigators to conduct team research across disciplines and institutions early in their careers focused on immuno-oncology and foster institutional cross-collaborations, the MRFBC is offering a 2 year young investigator team award of up to $150,000 per year ($300,000 total).The goals of the MRFBC-BMS Young Investigator Translational Immuno‐Oncology Team Science Award include 1) to help identify and support the next generation of melanoma scientists and 2) to focus on either improving clinical outcomes for patients with melanoma being treated with immuno‐oncology agents or advancing the scientific understanding of immuno‐oncology and the role of the immune system in melanoma.

Melanoma Meetings Around the World

  • April 2020, CURE OM Patient and Caregiver Symposium in Houston, Texas USA
  • June 18-21, 2020, 24th International Pigment Cell Conference in Yamagata, Japan