Uncovering the Mystery of Metastatic Dormancy in Breast Cancer: An Unprecedented View

ASPIRE Award (2020-2022)

Alana Welm, PhD, University of Utah

Alana Welm, PhD

Despite advances in treatments for breast cancer, metastatic breast cancer remains an incurable disease that results in 40,000 deaths per year in the US. Although some patients already have metastatic disease when they are first diagnosed, other cases of breast cancer recur and metastasize months or even years after an initial course of treatment that appeared to eradicate the primary tumor. Understanding where and how these tumor cells hide out and remain dormant for long periods of time, as well as how they are reactivated and why they are so resistant to therapy, is critical for developing new treatment strategies for this lethal disease. One of the critical challenges that has hindered the study of dormant tumor cells is the difficulty of accessing samples of these cells to study. To address these questions, the Welm lab has inaugurated a rapid autopsy program of patients with metastatic breast cancer to enable the direct study of these cells in their natural environment. Rapid autopsy is a coordinated effort in which pathologists and scientists work together to extract and analyze tissues from a patient shortly after death. Through the application of state-of-the-art genomics techniques and ex vivo patient-derived tumor modeling, the Welm lab will conduct the first characterization of active human breast cancer metastases in parallel with analysis of dormant tumor cells in the same individuals. This project will begin to answer questions about why some cancer cells stay dormant and why some grow into active metastases. It will also generate new hypotheses about how to prevent the outgrowth of dormant tumor cells that leads to cancer recurrence and death.

published research

Goddard ET, Linde MH, Srivastava S, Klug G, Shabaneh TB, Iannone S, Grzelak CA, Marsh S, Riggio AI, Shor RE, Linde IL, Guerrero M, Veatch JR, Snyder AG, Welm AL, Riddell SR, Ghajar CM. Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies. Cancer Cell. 2024.

Geukens T, Maetens M, Hooper JE, Oesterreich S, Lee AV, Miller L, Atkinson JM, Rosenzweig M, Puhalla S, Thorne H, Devereux L, Bowtell D, Loi S, Bacon ER, Ihle K, Song M, Rodriguez-Rodriguez L, Welm AL, Gauchay L, Murali R, Chanda P, Karacay A, Naceur-Lombardelli C, Bridger H, Swanton C, Jamal-Hanjani M, Kollath L, True L, Morrissey C, Chambers M, Chinnaiyan AM, Wilson A, Mehra R, Reichert Z, Carey LA, Perou CM, Kelly E, Maeda D, Goto A, Kulka J, Székely B, Szasz AM, Tőkés AM, Van Den Bogaert W, Floris G, Desmedt C. Research autopsy programmes in oncology: shared experience from 14 centres across the world. J Pathol. 2024.