The Prostate Cancer Microenvironment: Implications for Therapy

Christopher J. Logothetis, MD

In order to design new treatments for prostate cancer and prolong the lives of patients with the disease, researchers are going to have to delve into the tumor microenvironment. That was one of the key messages presented at the New Frontiers in the Management of Solid and Liquid Tumors conference held at the John Theurer Cancer Center at Hackensack University Medical Center in New Jersey.

Christopher J. Logothetis, MD, chair of the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, explained that long-accepted models of tumor progression are simply not holding up as we gain a better understanding of the microenvironment of prostate cancer.

Many cancers become more chemotherapy-resistant over time, so that chemotherapy is more effective in earlier stages. However, when cell signaling pathways are examined more closely, this model does not hold up in prostate cancer, Logothetis said.

Cell signaling can occur between nearby cells (paracrine signaling) or within the same cell (autocrine signaling). Both paracrine and autocrine signaling can result in tumor growth, with autocrine signaling usually occurring later than paracrine signaling in terms of disease progression. This is an important point because research has linked these signaling pathways to chemotherapy sensitivity and resistance. “Only when [the tumor] becomes autocrine…does it become chemotherapy sensitive,” Logothetis said.

Interaction of the paracrine and autocrine pathways also influences the organ-specific progression of the disease, evidenced by the fact that prostate cancer most commonly metastasizes to the bone, Logothetis said. It’s estimated that 90% of cases of advanced-stage prostate cancer metastasize to the bones.

Studies are now exploring the relationship of these pathways in epithelial tissue and the ability of the cancer to migrate from its origin in the prostate. Results so far indicate that stromal elements mediate paracrine support of the development of prostate cancer in the bone. In addition, separate studies have suggested that prostate stromal cells exhibit growth-promoting effects on malignant epithelial cells. These data suggest that prostate cancer cells in bones communicate with one another in such a way so as to control the progression of the disease.

A better understanding of the prostate cancer microenvironment is leading to more effective treatments, both through the improved use of existing treatments and the development of novel therapies.

For example, docetaxel, a chemotherapy agent approved for use in patients with metastatic prostate cancer who have failed prior chemotherapy, has been a standard treatment for advanced-stage disease. However, Logothetis said that oncologists should consider the use of serial chemotherapy, or successive chemotherapy delivered in doses corresponding to disease progression. By taking into account cell signaling pathways and an understanding of their impact on the sensitivity of tumors to chemotherapy, this serialized approach may have a greater impact on patient survival.

“Understanding the disease and applying the proper chemotherapy makes a difference,” Logothetis said.