Research

Project 1: Targeting Breast Cancer Stem Cells to Prevent Recurrence

Despite aggressive treatment regimens including surgery, radiation, and chemotherapy, breast cancer recurrence remains nearly universal, largely attributable to intratumoral heterogeneity and therapy-resistant Cancer Stem Cell (CSCs). As a rare subset possessing stem-like capabilities of self-renewal and multilineage differentiation, CSCs can regenerate the cellular diversity of tumors after therapies targeting bulk cancer cells. By evading elimination, residual CSCs are implicated as drivers of disease relapse and propagation. Developing therapeutic interventions that specifically eliminate CSCs represents an appealing strategy to improve long-term remission, requiring elucidation of mechanisms underlying their malignant transformation. Utilizing integrated molecular, biochemical, genomic and proteomic approaches, our lab is dissecting signaling pathways dysregulated in breast CSCs. We have further established interdisciplinary partnerships leveraging nanotechnology and mathematical modeling to illuminate CSC behaviors in vitro and in vivo while pioneering CSC-directed therapies.

Project 2: Developing Innovative Immunotherapies for Breast Cancer

The advent of cancer immunotherapy represents a seismic shift in oncological treatment paradigms. Strategically harnessing the immune system to mount durable anti-tumor responses has achieved remarkable success at scale. However, many breast cancers remain refractory to immune checkpoint blockade, underscoring the profound immunosuppression still shrouding such malignancies' tumor microenvironments (TMEs). While intensive efforts to reinvigorate intractable TMEs persist, emerging preclinical and clinical evidence makes clear a robust systemic immune response is equally essential for realizing immunotherapy's full potential. Yet coordination of local and systemic immunity governing breast cancer development and modulation by emerging immunotherapies remains poorly defined. Leveraging cutting-edge omics approaches, transgenic models and conditional knockouts, our lab is elucidating how tumor- and host-derived IL-1α fuels breast cancer progression by orchestrating immune deregulation. Our overarching goal is assessing novel strategies selectively targeting IL-1α to optimize immune system conditioning and thereby potentiate immunotherapy efficacy against breast malignancies. Our pioneering approaches promise to overcome immunotherapy resistance by synchronizing localized immune remodeling with host-wide immune activation.

Project 3. Harnessing the Gut Microbiome to Improve Breast Cancer Therapy

The extensive microbial communities occupying the human gut form mutualistic relationships with their hosts, profoundly shaping immune function. Capitalizing on such innate interkingdom dialogues, pioneering studies reveal certain commensal bacteria can optimize cancer immunotherapy outcomes. Clinical investigations demonstrate that increased abundances of specific gut microbes strongly correlate with improved immunotherapy responses in renal and lung cancer patients. However, analogous microbiome-mediated stimulation of anti-tumor immunity against breast cancer remains unexplored. Intriguingly, our preliminary data unveils specific commensal strains attenuating breast cancer progression and amplifying anti-tumor immune responses in murine models. We hypothesize defined gut microbes, and their bioactive metabolites can be strategically co-opted to boost immunotherapy and alleviate common chemo-immunotherapy adverse effects in breast cancer. Comprehensively profiling microbes associated with breast tumors and immunotherapies, including their secreted products and host interaction dynamics, will provide key insights into microbiome-immune interplay regulating treatment outcomes. Our overarching goal is integrating select bug-based compounds within existing chemo- and immune-therapeutic regimens to improve patient responses.

Publications

Hexin Chen - Bibliography