Dr. Kenneth Pienta Laboratory
MI-ONCOSEQ: Personalized oncology through integrative high-throughput sequencing
Lab: Targeting The Cancer Ecosystem
Current Clinical Trials
600 N. Wolfe Street , Marburg 121
The tumor ecosystem: Cancer as an invasive species
Ecologists have studied the population biology of invasive species for decades and have documented their impact on local environments as well as the global ecosystem as a whole. Invasive species start as a native population within a defined commu- nity and are then transported by some means to a new environment. In this new environment, the invader either then dies off or enters a period of time during which it establishes itself (lag period). It then begins to spread and have impact on the local environment, disrupting the ecosystem as a whole. This disruption has broad implica- tions for the native species and the broader ecosystem. Biologic traits that result in a robust invasive species include rapid proliferative capacity, adaptation to environ- mental stress (phenotypic plasticity) and high tolerance to environmental heterogeneity.
The life cycle of invasive species is directly analogous to the study of cancer metastasis [see Figure]. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate at a target organ (invasive species survival in trans- port). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period) before proliferating (invasive spread). Proliferation in the new site has an impact on the target organ microenvironment (ecological impact) and eventually the human host (biosphere impact).
Chen KW, Pienta KJ. Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles. Theor Biol Med Model. 2011 Oct 3;8:36
A large proportion of solid tumor metastases are bone metastases, known to usurp HSC hom- ing pathways to establish footholds in the bone marrow. Recent evidence suggests that tumor cells target and parasitize the HSC niche during metastasis just as invasive species do in the environment. Successful metastatic cancer cells grow in a primary site, emigrate out from that site, survive during migrate, immigrate into the new environment, and then naturalize and overtake / co-opt and / or cooperate with the host species to form a new tumor ecosystem
Prostate cancer as an invasive species
Pienta KJ, Loberg R. The "emigration, migration, and immigration"of prostate cancer. Clin Prostate Cancer. 2005 Jun;4(1):24-30.