Ecosystem Re-engineering, Restoration Ecology, and “Eco-therapies”

“You have an environment and ecosystem in which you want to wipe out an invasive species,” Dr Verbridge said. “Chemo drugs just try to take out individual members of that species, 1 by 1. That’s the traditional treatment paradigm.”


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But by seeking instead to fine-tune the invasive species’ ecology, figuring out its food base and the interactions that sustain it, researchers might be able to drain the swamp, halting local tumor progression, and perhaps preventing metastasis. That is very similar to how restoration ecologists try to rebuild damaged natural ecosystems.

Most of Dr Amend’s tumor ecology research focuses on the cancer cell, but other cell species are “critical players in the cancer ecosystem,” she emphasized. “Secondary invaders into the cancer swamp include tumor-associated macrophages and cancer-associated fibroblasts, both which positively contribute to tumor growth. Other important cell species include host immune cells that act as predators to kill cancer cells.”

Examining each component of the tumor ecosystem should provide new avenues of research and development for novel therapies for patients with breast cancer and other malignancies, Dr Amend said.

Many “restoration ecology” treatment approaches are already in clinical use, Dr. Amend noted. Ablation of oligometastases via radiation or surgery is one example. Other approaches are under preclinical and clinical study.

The “prototypical example of a successful eco-therapy” is bone marrow transplant, a standard of care for patients with some types of leukemia and multiple myeloma, Dr Amend said. “In these cases, the ‘cancer swamp’ has completely taken over the native ecosystem. Irradiation and bone marrow transplant destroys the cancer ecosystem and restores the native ecosystem, leading to effective cures or long-term remission in those patients.”

Asked how tumor ecology research will be translated into new treatment options Dr Rosen said, “my feeling is you can’t just target signaling pathways alone. You have to approach this with other approaches.”

Nor should researchers rely on tumor shrinkage as a central endpoint, because that approach fails to consider the heterogeneous subpopulations—and resulting evolutionary potential—at play in many tumors, Dr Rosen said. “Just slowing the growth of a tumor or decreasing its size is insufficient. You have to look at what’s still in the tumor.”

Many preclinical studies look only at Response Evaluation Criteria in Solid Tumors (RECIST) criteria, but that too fails to address intratumoral heterogeneity and communication networks, and therefore the probability of recurrence and relapse.

Nor should ecosystem-inspired treatments be the only goal, Dr Verbridge added: “We need to understand cancer prevention better.”

Inhibiting tumorigenesis altogether likely has the greatest potential for curbing cancer mortality. But slowing tumor progression will also save lives.

“We know that cancer is treatable at the primary tumor stage,” he said. “If we can avoid it getting to the metastatic stage, then that’s the holy grail.”

Reference

  1. Rosen JM, Polyak K, Isacke CM. The tumor ecosystem. 39th San Antonio Breast Cancer Symposium; December 2016; San Antonio, TX.