Moffitt Cancer Center

The Center for Quantitative Delta Ecology and Evolution

sponsored by Cancer Systems Biology Consortium
Alexander Anderson, PhD

Alexander Anderson, PhD

Director

Robert Gatenby, MD

Robert Gatenby, MD

Co-Director

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Tumors are not simply collections of mutated cells that grow in isolation; rather, they respond to and modify both the physical microenvironment and a variety of host cells in the organ they are invading. These changes in ecology (“∆-Ecology”) are key to understanding tumor progression and the response to therapy – particularly the development of resistance. We focus on NSCLC, the most common and among the most lethal of human cancers and will define the ecological and evolutionary dynamics that govern disease progression and treatment, with the goal of driving novel therapeutic strategies that exploit this ∆-Ecology.



Research Goals Initiatives

Delta immune Ecology of NSCLC

Project 1 studies tumor-immune ∆-Ecology in KRAS-mutant NSCLC. Using computational image analysis of biopsies, we identify ecological patterns predicting immunotherapy response and resistance. KRAS-G12C inhibitors alter immune ecology, enabling combination therapies. Our goal: predictive ∆-Ecology models for novel treatment strategies in clinical trials.

Delta Stromal Ecology of NSCLC

Project 2 investigates stromal compartment changes during ALK/KRAS therapy resistance acquisition. We'll characterize temporal and spatial phenotypic changes in tumor-stromal interactions using in silico models. Through experimental validation, we'll develop combination therapy strategies for long-term remission in NSCLC models.

Outreach & Education

The Education Core hosts annual intensive workshops (IMO Workshop) training next-generation cancer researchers. Teams develop quantitative models and pilot proposals, with $50K awards for best applications. We offer internships, exchange programs, and public outreach to advance cancer systems biology education.

Ecological Core

The Ecological Core develops spatial models to study tumor-microenvironment interactions and ∆-Ecology over time. We manage high-resolution histology images and create computational frameworks to understand tumor heterogeneity, supporting both NSCLC projects to guide therapeutic strategies.

Mathematical Core

The Mathematical Modeling Core develops mathematical models to understand tumor ecology changes during initiation, progression, and therapy. Using spatial agent-based and non-spatial models, we bridge clinical and experimental data gaps, create virtual trials, and provide insights into ecological processes.

Evolutionary Therapy

In partnership with the Center of Excellence for Evolutionary Therapy, which helps develop personalized cancer treatments using evolutionary principles and math modeling to overcome drug resistance. Its goals align with the Delta Ecology Center by using mathematical models to understand cancer dynamics.

Center Research & Faculty CSBC

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Publications Publications

PSA/testosterone ratio as a potential biomarker to identify early progressors of adaptive therapy in metastatic castration sensitive prostate cancer.

Jill A Gallaher, Robert A Gatenby, Joel S Brown, Alexander R A Anderson, Jingsong Zhang

medRxiv

Mathematical Oncology: How Modeling Is Transforming Clinical Decision-Making.

Kevin R. Scibilia, Kit Gallagher, M.A. Masud, Mark Robertson-Tessi, Chandler D. Gatenbee, Jeffrey West, Paul Llamas, Sandhya Prabhakaran, Jill Gallaher, Alexander R.A. Anderson

Cancer Research

Modeling tumors as complex ecosystems.

Guim Aguadé-Gorgorió, Alexander R.A. Anderson, Ricard Solé

iScience

Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial.

Roger Li, Nancy Y. Villa, Xiaoqing Yu, Joseph O. Johnson, Gustavo Borjas, Jasreman Dhillon, Carlos M. Moran-Segura, Youngchul Kim, Natasha Francis, Denise Dorman et al.

Nature Medicine

Distinct Tumor-Immune Ecologies in Patients with Lung Cancer Predict Progression and Define a Clinical Biomarker of Therapy Response.

Sandhya Prabhakaran, Chandler D. Gatenbee, Mark Robertson-Tessi, Zarifa Gahramanli Ozturk, Theresa A. Boyle, Jhanelle E. Gray, Scott J. Antonia, Robert A. Gatenby, Amer A. Beg, Alexander R.A. Anderson

Cancer Research

A novel combination therapy for ER+ breast cancer suppresses drug resistance via an evolutionary double-bind.

Rena Emond, Jeffrey West, Vince Grolmusz, Patrick Cosgrove, Aritro Nath, Alexander R A Anderson, Andrea H Bild

BioRxiv

75 Years of Mathematical Oncology.

Franco Pradelli, Maximilian Strobl, Sadegh Marzban, François de Kermenguy, Ari Barnett, Katyayni Ganesan, Guillermo Lorenzo, David A. Hormuth II, Sara Hamis, Dhananjay Bhaskar, Alexander R. A. Anderson, Jeffrey West

BioRxiv

The impact of normal tissue density on tumor growth and evolution in a 3D whole-tumor model of lung cancer.

Rafael R Bravo, Mark Robertson-Tessi, Scott Antonia, Jhanelle Gray, Amer Beg, Robert Gatenby, Matthew B. Schabath, Alexander R A Anderson

BioRxiv

Evolutionary antifragile therapy.

Jeffrey West, Bina Desai, Maximilian Strobl, Jill Gallaher, Mark Robertson-Tessi, Andriy Marusyk, Alexander R. A. Anderson

BioRxiv

Evolutionary Double-Bind Treatment Using Radiation Therapy and Natural Killer Cell-Based Immunotherapy in Prostate Cancer.

Kimberly A. Luddy, Jeffrey West, Mark Robertson-Tessi, Bina Desai, Andrew Ojeda, Hannah Newmana, Veronica Estrella, Taylor M. Bursella, Sarah Barrett, Jacintha O’Sullivan, Laure Marignol, Robert A. Gatenby, Joel S. Brown, Alexander R.A. Anderson, Cliona O’Farrelly

International Journal of Radiation Oncology, Biology, Physics

The adaptive state determines the impact of mutations on evolving populations.

Roger Li, Nancy Y. Villa, Xiaoqing Yu, Joseph O. Johnson, Gustavo Borjas, Jasreman Dhillon, Carlos M. Moran-Segura, Youngchul Kim, Natasha Francis, Denise Dorman, John J. Powers, Wade J. Sexton, Philippe E. Spiess, Michael A. Poch, Logan Zemp, Scott M. Gilbert, Jingsong Zhang, Julio M. Pow-Sang, Alexander R. A. Anderson, Tingyi Li, Xuefeng Wang, G. Daniel Grass, James M. Burke, Colin P. N. Dinney, Paulo C. Rodriguez, Rohit K. Jain, James J. Mulé & Jose R. Conejo-Garcia

Proceedings of the National Academy of Sciences

The Hallmarks of Cancer as Eco-Evolutionary Processes.

Ranjini Bhattacharya, Stanislav S. Avdieiev, Anuraag Bukkuri, Christopher J. Whelan, Robert A. Gatenby, Kenneth Y. Tsai, Joel S. Brown

Cancer Discovery

A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis.

Ranjini Bhattacharya, Joel S. Brown, Robert A. Gatenby, Arig Ibrahim-Hashim

Seminars in Cancer Biology

Directed Evolution Restored Castrate Sensitivity in a Patient With Castrate Resistant Metastatic Prostate Cancer.

Robert A. Gatenby, Alexander R. A. Anderson, Joel S. Brown, Jill Gallaher, Jeffrey Krolick, Dawn Lemanne

The Prostate

Hyper Diversity, Species Richness, and Community Structure in ESS and Non-ESS Communities.

Kailas Shankar Honasoge, Tania L. S. Vincent, Gordon G. McNickle, Roel Dobbe, Kateřina Staňková, Joel S. Brown, Joseph Apaloo

Dynamic Games and Applications

Tumor Angiogenesis May Be A Tragedy of the Commons.

Ranjini Bhattacharya, Anuraag Bukkuri, Robert A. Gatenby, Joel S. Brown

Available at SSRN

Deriving Optimal Treatment Timing for Adaptive Therapy: Matching the Model to the Tumor Dynamics.

Kit Gallagher, Maximilian A R Strobl, Alexander R A Anderson, Philip K Maini

Bulletin of Mathematical Biology

Multifactorial stroma-mediated resistance is a major contributor to residual disease under targeted therapies in lung cancers.

Bina Desai, Tatiana Miti, Sandhya Prabhakaran, Daria Miroshnychenko, Menkara Henry, Viktoriya Marusyk, Pragya Kumar, Hilal Ozakinci, Chandler Gatenbee, Marilyn Bui et al.

Research Square

To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy.

Maximilian A R Strobl, Alexandra L Martin, Jeffrey West, Jill Gallaher, Mark Robertson-Tessi, Robert Gatenby, Robert Wenham, Philip K Maini, Mehdi Damaghi, Alexander R A Anderson

Cell systems

Cellular adaptation to cancer therapy along a resistance continuum.

Maayan Baron, Benjamin R King, Jozef P Bossowski, Alicia Bjornberg, Maayan Pour, Anjali Rao, Ayushi S Patel, Selim Misirlioglu, Dalia Barkley, Kwan Ho Tang et al.

Nature

Spatial interactions modulate tumor growth and immune infiltration.

Sadegh Marzban, Sonal Srivastava, Sharon Kartika, Rafael Bravo, Rachel Safriel, Aidan Zarski, Alexander R A Anderson, Christine H Chung, Antonio L Amelio, Jeffrey West

NPJ Systems Biology and Applications

Second-Order Effects of Chemotherapy Pharmacodynamics and Pharmacokinetics on Tumor Regression and Cachexia.

Luke Pierik, Patricia McDonald, Alexander R. A. Anderson, Jeffrey West

Bulletin of Mathematical Biology

Mathematical Model-Driven Deep Learning Enables Personalized Adaptive Therapy.

Kit Gallagher, Maximilian AR Strobl, Derek S Park, Fabian C Spoendlin, Robert A Gatenby, Philip K Maini, Alexander RA Anderson

Cancer Research

Spatial interactions modulate tumor growth and immune infiltration.

Sadegh Marzban, Sonal Srivastava, Sharon Kartika, Rafael Bravo, Rachel Safriel, Aidan Zarski, Alexander Anderson, Christine H Chung, Antonio L Amelio, Jeffrey West

Research Square

A gene for all seasons: The evolutionary consequences of HIF-1 in carcinogenesis, tumor growth and metastasis.

[Authors to be added]

Seminars in Cancer Biology

Dissecting the Spatially Restricted Effects of Microenvironment-Mediated Resistance on Targeted Therapy Responses.

Tatiana Miti, Bina Desai, Daria Miroshnychenko, David Basanta, Andriy Marusyk

Cancers

Modeling tumors as species-rich ecological communities.

Guim Aguadé-Gorgorió, Alexander R. A. Anderson, Ricard Solé

bioRxiv

Tumor-immune metaphenotypes orchestrate an evolutionary bottleneck that promotes metabolic transformation.

Jeffrey West, Frederika Rentzeperis, Casey Adam, Rafael Bravo, Kimberly A Luddy, Mark Robertson-Tessi, Alexander R A Anderson

Frontiers in Immunology

A novel combination therapy for ER+ breast cancer suppresses drug resistance via an evolutionary double-bind.

Rena Emond, Jeffrey West, Vince Grolmusz, Patrick Cosgrove, Aritro Nath, Alexander RA Anderson, Andrea H Bild

bioRxiv

Antifragility as a complex system's response to perturbations, volatility, and time.

Cristian Axenie, Michail A Makridis, Meisam Akbarzadeh, Matteo Saveriano, Alexandru Stancu, Jeffrey West

ArXiv

Spatial interactions modulate tumor growth and immune infiltration.

Sadegh Marzban, Sonal Srivastava, Sharon Kartika, Rafael Bravo, Rachel Safriel, Aidan Zarski, Alexander Anderson, Christine H Chung, Antonio L Amelio, Jeffrey West

bioRxiv

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