Targeting dormant breast cancer cells in the bone: Is suppression a viable option?

Targeting dormant breast cancer cells in the bone: Is suppression a viable option?

Live Webinar: 22 April 2021, 4 pm CET 

Organised by ECTS

Date & Time: 22 April 2021, 4 pm CET

Featuring Rachelle Johnson, and moderated by Jessica Pepe

Costs: Live webinar is free for ECTS members and non-members, but a registration is required. Recordings are accessible to ECTS members only.

Format:

• 5 min welcome & introductions
• 35 min presentation on ” Targeting dormant breast cancer cells in the bone: Is suppression a viable option?”
• 20 min Q&A

Learning Objectives:

• Understand the major molecular and cellular mediators that regulate breast cancer emergence from dormancy in the bone
• Identify the advantages and drawbacks of therapeutic strategies for targeting dormant, disseminated tumor cells
• Recognize the potential need for combination anti-resorptive therapies when targeting bone-disseminated tumor cells

The Cancer-cell dormancy, Brussels, Belgium, 22-04-2021 has been accredited by the European Accreditation Council for Continuing Medical Education (EACCME®) with 1 European CME credits (ECMEC®s).

Each medical specialist should claim only those hours of credit that he/she actually spent
in the educational activity.”

Featuring Dr. Rachelle Johnson

Dr. Johnson earned her doctorate in Cancer Biology from Vanderbilt University, where she studied bone metastatic breast cancer with Drs. Gregory Mundy and Julie Sterling in the Vanderbilt Center for Bone Biology. She then relocated to Melbourne, Australia to pursue a post-doc with Drs. Natalie Sims and T. John (Jack) Martin in basic bone biology to better understand the physiological processes of skeletal homeostasis that may impact upon tumor cells. As a postdoc in Melbourne, she characterized the skeletal phenotype of several glycoprotein-130 (gp130) and SOCS3 (a gp130 downstream target) bone conditional knockout mouse models. She then joined Dr. Amato Giaccia’s laboratory as a Postdoctoral Scholar at Stanford University, where she examined the role for leukemia inhibitory factor (LIF) receptor (LIFR) in tumor dormancy. She returned to Vanderbilt University Medical Center as faculty in 2016, where her lab now studies mechanisms of tumor dormancy in bone. Dr. Johnson is an active member of and holds leadership positions in the American Society for Bone and Mineral Research (ASBMR) and the Cancer and Bone Society (CABS). She has received the ASBMR Young Investigator Award, AIMM-ASMBR John Haddad Young Investigator Award, ANZBMS Kaye Ibbertson Award for Bone and Mineral Medicine, and the ASBMR Harold M. Frost Young Investigator Award. She was also the recipient of an NIH Pathway to Independence Award from the National Institutes of Health (NIH)/NCI.

Her current work is focused on the mechanisms driving tumor cell dormancy in bone and the molecular processes that enable disseminated tumor cells to colonize the bone. In particular, she is interested in the role of leukemia inhibitory factor (LIF) signaling, parathyroid hormone-related protein (PTHrP), and hypoxia signaling in breast cancer dissemination and outgrowth in the bone marrow.

Moderated by Jessica Pepe

Jessica Pepe MD, PhD is an Assistant Professor of Internal Medicine in the Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Faculty of Medicine and Dentistry, “Sapienza” University of Rome.

After her specialization in internal medicine, she obtained a PhD in pathophysiology and diseases of the skeletal system at the “Sapienza” University of Rome and she went for a post-doc at the Service of Bone Diseases, Geneva University Hospital and Faculty of Medicine in Switzerland.

She has authored and co-authored more than 120 articles in international peer-reviewed journals. Her research is focused on osteoporosis, vitamin D and primary hyperparathyroidism.

Breast cancer cells frequently disseminate to the bone marrow, where they may either enter a dormant state or colonize the bone and induce osteolysis. The mechanisms that regulate tumor cell entry and exit from dormancy in the bone are not well understood, but several factors have been identified. Previous work from our group found that leukemia inhibitory factor receptor (LIFR) promotes tumor dormancy when expressed on bone-disseminated tumor cells and that loss of LIFR enables otherwise dormant tumor cells to colonize the bone. Our lab has therefore examined how LIFR expression is regulated in breast cancer cells, with the hope that understanding its regulation might provide novel avenues to therapeutically target dormant disseminated tumor cells. Through these efforts we have found that LIFR is epigenetically regulated, and that histone deacetylase (HDAC) inhibitors, which are FDA-approved for several blood cancers, stimulate LIFR expression on breast cancer cells from all subtypes. This finding presents an interesting therapeutic opportunity to explore whether HDAC inhibitors may be used to promote a chronic state of tumor dormancy and prevent recurrence in bone. Our findings suggest that this may be feasible, but that the effects of histone deacetylase inhibitors on bone remodeling profoundly impact tumor colonization and must be combined with appropriate anti-resorptive therapies.