2021 Special Pledge

Small Cell Lung Cancer Research at Fox Chase Cancer Center

What is Small Cell Lung Cancer?

Small Cell Lung Cancer (also called "SCLC") is the most lethal type of lung cancer. The uniqueness of this tumor consists of an initial exquisite response to chemotherapy. However, at relapse, which occurs early in the majority of patients, the tumor is resistant to all available therapies and will eventually cause a premature death of the patient in less than 12 months. SCLC tumors contain different subpopulations of cancer cells, a feature known as tumor heterogeneity. While cell heterogeneity is a key determinant of cancer progression and drug resistance, how it impacts the immune system in SCLC patients remains incompletely defined. We recently identified a group of genetic elements known as Endogenous Retroviruses (ERVs) that are altered in certain drug-resistant populations of SCLC cells. We showed that signaling from these ERVs promotes tumorigenesis, but that these retroviruses can also make cancer cells vulnerable to immunotherapy. This proposal seeks to study the biology that connects this drug-resistant cancer cell state in SCLC to the activation of ERVs, and to use these insights to develop therapeutic strategies that enhance response to immunotherapy. We aim to perform genetic screens to identify regulators that control these ERVs in drug-resistant lung cancer cells. Ultimately, the use of a novel 3D culture technology using human lung cancer specimens will allow us to determine the most effective therapeutic combinations and personalize immunotherapy. The knowledge gained in the course of this research proposal will not only uncover completely new biology of this malignancy, but may directly provide new and attractive therapeutic strategies to favor responsiveness to immunotherapy and ultimately improve outcomes for SCLC patients.

More from Dr. Canadas: With this important support we will investigate novel therapeutic strategies to restore tumor immunogenicity and influence responsiveness to immunotherapy in lung cancer, with a particular interest in poorly immunogenic tumors, such as Small Cell Lung Cancer. 

Specifically, this fund will allow us to use CRISPR-Cas9 screens (“gene-editing” screens) in multiple human lung cancer cell lines, couple with state-of-the-art transcriptomics and epigenetics approaches to identify novel regulators able to enhance anti-tumor immunity and favor response to immunotherapy. In addition, this will help us to develop a novel and sophisticated tumor organoid system using human primary lung tumors to validate promising therapeutic combinations in an ex vivo cell culture system that incorporates features of the tumor microenvironment and models the dynamic response to immunotherapy.

The knowledge gained in the course of this research will not only provide insights into fundamentally important biology in lung cancer, but may help to identify future novel combination therapies that will expand the breadth and depth of response to immunotherapy, helping to reach the ultimate goal of my laboratory: to discover and validate new therapeutic opportunities to improve lung cancer patient health.

Thank you to our Special Pledge Donors

Diamond Level
Anonymous
David and Sandy Marshall made a pledge In Honor of  Denise Jill Marshall


Ruby Level
Anonymous made a pledge In Memory of Joseph F. Riggione Jr. 
Morel Family Foundation
Jim and Sue Anderson
Sniger Family Charitable Trust 
Lisa and Jon Otto

Sapphire Level
Lou and Carol Della Penna
Lillian O'Connor
J&J Matching Gifts
David and Robin Wiest


Emerald Level
Jim and Rhea Brown
Addie Riggione made a pledge In Memory of Joe Riggione
Rick and Flo Celender
Richard B. Millham, Sr made a pledge In Memory of Anita Nyari
John Megget
Norman and Winnie Troxel
James Flynn and Susan Johnson
Michael and Jean Fowler
Lee and Ginny Beyer
R & R Wood Products, Inc
Kim LaGueux made a pledge In Memory of Barbara Grigg Moses and Scott Lee Grigg


Opal Level
Lore and Robert Eichfeld
Re/MAX Properties-Newtown made a pledge In Memory of John O'Donnell
Mr. and Mrs. Christopher B. Chandler made a pledge In Memory of Dorothy Burrage Chandor 
Linda Sterthous & Anna Kruschwitz made a pledge In Memory of John O'Donnell, our beloved Brother-in-Law
Lucy Dailey
Allison Zimmerman
Liz Rizor made a pledge In Honor of Carol and Louis Della Penna
SpectrumMetals, Inc made a pledge In Memory of John O'Donnell
Dr. Paul and Janet Engstrom
Graham Peterson made a pledge In Memory of John O'Donnell
Donna Schuman
Bill and Rose Gruccio
Duane Perry and Arthur Kaplan made a pledge In Memory of John O'Donnell
Anonymous made a pledge In Honor of  Lillian O'Connor


Amethyst Level
Denise Marshall
Megan Officer made a pledge In Memory of Uncle John O'Donnell
Mal Singerman made a pledge In Memory of Edward F. O'Connor
Bill and Georgia Ford
Barbara O'Donnell made a pledge In Memory of John V. O'Donnell 
Hunter and Kristin Doble made a pledge In Memory of John O'Donnell
Kim Gronendahl made a pledge In Memory of Dutch Gronendahl 
Barbara and Bruce Franzel made a pledge In Memory of John O'Donnell
Kathleen O'Donnell made a pledge In Memory of John O'Donnell 
Heller's Seafood Market
C&N
Andrew and Ellen Schindler

Garnet Level
Anonymous made a pledge In Honor of Lillian O'Connor
Sean O'Donnell made a pledge In Memory of John O'Donnell
Sandra Sterthous and Brian Powell made a pledge In Memory of John O'Donnell
Kathleen Campbell made a pledge In Memory of John O'Donnell
Daniel J. McClosky made a pledge In Memory of John O'Donnell
Walter J. Young made a pledge In Memory of Pauline Young & Margaret Walsh
Tyma Trachtenberg Dental
Joe O'Donnell made a pledge In Memory of John O'Donnell
Margaret and John Abbott made a pledge In Memory of John O'Donnell
Linda and John Brown
John and Jane Delp made a pledge In Honor of Donna Schuman
Lynn Martin Haskin
Carolyn Kozakowski
Ryan and Julie O'Donnell made a pledge In Memory of John O'Donnell
Phillip and Susan Zaks made a pledge In Honor of Donna Schuman
David and Wendy Rees
Brian Gallagher made a pledge In Memory of John O'Donnell
Casey Heim and Kevin O'Donnell made a pledge In Memory of John O'Donnell
Charlotte and Kevin Keenan
Helen Leonard made a pledge In Memory of John O'Donnell 
Lynda Wayne of Cadence Hearing Services LLC made a pledge In Memory of John O'Donnell 
Kermit and Georgianna Kemp
Jane G. Thomas made a pledge In Memory of Benjamin M. Thomas III
Charlotte Wilkins made a pledge In Honor of Lillian O'Connor
Charlotte Wilkins
Maureen Riley made a pledge In Memory of John O'Donnell
George Kettelberger
Steven and Joyce Hanson
Randal Reich made a pledge In Memory of Barbara Moses
William and Rosemary Gruccio made a pledge In Honor of Robert Kane

Your Choice Pledge 
Eileen and Kevin O'Rourke made a pledge In Memory of John O'Donnell
Jim and Mary Borthwick
Carol A. Resch made a pledge In Memory of John O'Donnell
Rosemary and Niles Hall made a pledge In Memory of John O'Donnell
Janice Hudson made a pledge In Memory of John O'Donnell
Fran Collins made a pledge In Memory of John O'Donnell
Joseph O'Donnell made a pledge In Memory of John O'Donnell
Margaret Donahue made a pledge In Memory of John O'Donnell
James Garvey made a pledge In Memory of John O'Donnell
Diane Sterthous made a pledge In Memory of John O'Donnell
Jane Thomas made a pledge In Memory of William and Betty Lopatin
Nancy Hall made a pledge In Memory of John O'Donnell
Janice Kimenhour


In Kind Donation
Doylestown Historical Society