Prevention and treatment of metastatic disease is one of the most difficult challenges facing cancer treatment. While our knowledge of metastatic disease has grown significantly, precise therapies to intervene early and stop metastasis are not available. The discovery that disseminated cancer cells (DCCs) or even recurrent clones in hematological malignancies can originate very early in cancer evolution and that early or late evolved systemically disseminated clones can enter years- to decades-long periods of dormancy, reshaped our notion of metastasis targeting. For the first time, we gained insight into an unexpected biology: that cancer pauses its progression, revealing a window of opportunity for early intervention.
The Cancer Dormancy & Tumor Microenvironment Institute (CDTMI) is the first to integrate an orthogonal approach to address how residual cancer dormancy, aging, lifestyle-related perturbations of target organ niches, epigenetics, genetics, and treatments influence relapse across all cancers.
The CDTMI combines exploration of cancer dormancy and metastasis, evolutionary biology, age-related tissue pathologies like clonal hematopoiesis, adaptive and innate immunity, and adult stem cell quiescence in tissue microenvironments across solid cancer and hematological malignancies.
We collaborate with other institutes and Centers of Excellence at Montefiore Einstein to leverage technological advancements and knowledge across disciplines not immediately obvious to the problem of cancer dormancy and relapse to foster a multidisciplinary and innovative institute with a transformative impact.
Vision & Mission
Our vision pursues a model of integrated and collaborative science. This complementation enables an unsurpassed level of integration, co-experimentation, and cross-fertilization of ideas and communication to address and solve the problem of cancer dormancy and relapse.
Our hypothesis is that residual dormant cancer cells persist after therapy and/or populated target organs long before clinical relapse due to early spread. We posit that residual cancer cells are kept dormant by the same homeostatic signals and cell types that instruct adult stem and differentiated cells to maintain orderly repair and restricted growth patterns. We envision that as we age and/or perturb those homeostatic programs in ways that mimic aging-related damage, heterogeneous dormant residual cancer cell sub-populations may become reactivated and form metastases in sold cancer or systemic recurrent in hematological malignancies. The timing of these microenvironment-driven transitions may be further influenced by the transcriptional and/or epi/genetic "maturity" of DCCs. The programs at the CDTMI aim to solve this puzzle by identifying the host- and residual cancer cell-specific mechanisms that induce and maintain dormancy but, when disrupted, can fuel reactivation.
We take advantage of remarkable technological advances in genome editing, transgenic animal models, proteomics, metabolomics, engineering, intravital and whole-body imaging, single-cell profiling and spatial transcriptomics that allow biological systems to be probed and manipulated with unprecedented resolution.
As a multidisciplinary Institute, we're optimally positioned to combine expertise in medical oncology, epidemiology, cell biology, evolutionary biology, aging, immunology, hematopoiesis, engineering, optical subcellular and whole-body imaging, and computational biology along with patient advocates. It's a big vision for delivering new biomarkers and therapeutic strategies.
Significantly, the CDTMI will participate in the MECC programs of community outreach and engagement (COE) to create a space of communication and education with patient advocates and the community to fine-tune our science with a patient-centered perspective.
- To identify the intrinsic and tumor microenvironment mechanisms that control cancer dormancy
- To determine how changes in the host contribute to awakening of dormant cancer cells
- Study the effect of aging on cancer dormancy and its relationship with the immune system
- Identify dormancy biomarkers and therapeutics to kill dormant cells or maintain dormancy
Julio Aguirre-Ghiso, Ph.D.
Director, Institute for Cancer Dormancy & Tumor Microenvironment
Institute founder and Director, Endowed Professor Julio Aguirre-Ghiso, Ph.D., is also the Co-Leader of the MECC's Tumor Microenvironment and Metastasis Program and Director of the Gruss Lipper Biophotonics Center. He is President of the Metastasis Research Society and has served at several leadership levels at AACR.
Dr. Aguirre-Ghiso’s research team is focused on understanding the biology of residual cancer cells that persist in a dormant state after initial therapy—findings that represent a paradigm shift from the long-held notion that cancer is perpetually proliferating. Applied in clinical studies, these findings are uncovering ways to maintain residual cancer dormancy, kill dormant cancer cells, and utilize markers to determine the dormant or active state of disseminated cancer cells. Published in top-tier journals such as Nature, Nature Cell Biology, Science, and Cancer Cell, these discoveries have prompted Dr, Aguirre-Ghiso to found HiberCell, a company now conducting clinical trials and furthering drug development born from his breakthroughs in the lab.
The CDTMI has recruited 36 Montefiore Einstein faculty members to join the Institute.
Research Themes and Areas of Focus
We hypothesize that dormancy states of early or late evolved disseminated cancer cells (DCCs) in solid cancers (B) or residual cancer cells in hematological malignancies (C) are affected by common but also distinct alterations of target organs niches (A & D) caused by aging, senescence and, among others, inflammatory processes that may create dysfunctional adult stem cell niches and loss of tissue homeostasis (A). Alone or in addition to these changes, bone marrow (BM)-originating alterations such as fibrosis, now coupled with genetic alterations in the cancer cells and/or lifestyle-led changes in target organs that alter the crosstalk between distinct niches and dormant cancer cells could cause their reactivation (A). Our focus is on cancers and sites where we have documented early and late dissemination and dormancy of these early and late evolved DCCs in genetically engineered mouse models and/or patients (B) and in hematological malignancies where minimal residual disease and relapse are a major problem (B). Our focus is also on target organs where recurrences can emerge across these cancers such as the brain, lung, liver, lymph nodes and bone marrow. The CDTMI membership, which is being expanded by an active recruitment effort (see recruitment tab) brings together complementary expertise in the host variables (colored circles from A) and cancer models (B & C) described here.
The Institute’s translational focus is also supported by our ability to access relevant human samples via a close collaboration with NYPOG to ask questions about dormancy and metastasis in fresh bone marrow aspirates and lymph node samples, among others, to isolate DCCs and host cells for profiling, FFPE primary and metastatic tissues to validate markers and complement DCC analysis as well as normal host tissue to interrogate the effect of the variables in panel A on the target organ niches that induce dormancy of cancer cells.
The CDTMI Advisory Board includes Drs. Julio Aguirre-Ghiso, Edward Chu, Ulrich Steidl, Amit Verma, Maja Oktay, Alyson Moadel-Roblee, and John Condeelis. Over time, it will name additional advisory board members with basic, translational, and clinical expertise from MECC as well as outside experts that will help guide the Institute's mission and growth.
Advocates & Community Involvement
We aim to involve a racially, economically, geographically, and culturally diverse group of Bronx-based community members and patient advocates in the activities of our research program–to benefit everyone involved. The community will be involved in helping to introduce the CDTMI to the community, especially to individuals and groups who have been historically underrepresented in cancer care and disproportionately affected by metastatic disease.
Under the leadership of Alyson Moadel-Robblee, Ph.D., CDTMI coordinates activities related to education, communication, metastatic cancer patient support groups, and community engagement that will both inform and disseminate the work done at our Institute. Dr. Moadel-Robblee is a Professor of Clinical Epidemiology at the Albert Einstein College of Medicine who serves as the MECC Director of Community Engagement and Health Equity and Founding Director of the Bronx Oncology Living Daily (BOLD Living) Cancer Wellness Program.
The CDTMI is recruiting talented investigators in the biological and biomedical sciences with research programs aligned with the Institute’s vision. The call for faculty positions is open at the Assistant and Associate Professor levels. Interested candidates should send a summary of their research program and goals and curriculum vitae to Nuri Panjaton at email@example.com.