Phase I clinical study of heptaplatin (H) and paclitaxel (P) in previously treated patients with advanced solid tumor

Traditionally, prostate cancer treatment, as well as all cancer treatment, has been designed to target the tumor cell directly via various hormonal and chemotherapeutic agents. Recently, the realization that cancer cells exist in complex microenvironments that are essential for the tumorigenic and metastatic potential of the cancer cells is starting the redefine the paradigm for cancer therapy. The propensity of prostate cancer cells to metastasize to bone is leading to the design of novel therapies targeting both the cancer cell as well as the bone microenvironment. Tumor cells in the bone interact with the extracellular matrix, stromal cells, osteoblasts, osteoclasts, and endothelial cells to promote tumor-cell survival and proliferation leading to a lethal phenotype that includes increased morbidity and mortality for patients with advanced prostate cancer. Several strategies are being developed that target these complex tumor cell-microenvironment interactions and target the signal transduction pathways of other cells important to the development of metastases, including the osteoclasts, osteoblasts, and endothelial cells of the bone microenvironment. Current and new therapies in metastatic prostate cancer will comprise a multitargeted approach aimed at both the tumor cell and the tumor microenvironment. Here, we review the current therapeutic strategies for targeting the prostate cancer-bone microenvironment and several single- and multiagent targeted approaches to the treatment of advanced prostate cancer that are under development.

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Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype

Loberg

Logothetis

Keller

et al. 2005

JCO

132

100

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Are Vaccines Making a Comeback in Non–Small-Cell Lung Cancer?

Nemunaitis

2008

JCO

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Paradigm Shifts in Cancer Vaccine Therapy

Schlom

Gulley

Arlen

2008

Exp Biol Med (Maywood)

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Cancer vaccines constitute a unique therapeutic modality in that they initiate a dynamic process involving the host's immune response. Consequently, (a) repeated doses (vaccinations) over months may be required before patient clinical benefit is observed and (b) there most likely will be a "dynamic balance" between the induction and maintenance of host immune response elements to the vaccinations vs. host/tumor factors that have the potential to diminish those responses. Thus "patient response" in the form of disease stabilization and prolonged survival may be more appropriate to monitor than strictly adhering to "tumor response" in the form of Response Criteria In Solid Tumors (RECIST) criteria. This can be manifested in the form of enhanced patient benefit to subsequent therapies following vaccine therapy. This article will review these phenomena unique to cancer vaccines with emphasis on prostate cancer vaccines as a prototype for vaccine therapy. The unique features of this modality require the consideration of paradigm shifts both in the way cancer vaccine clinical trials are designed and in the way patient benefit is evaluated.

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Phase I clinical study of heptaplatin (H) and paclitaxel (P) in previously treated patients with advanced solid tumor

Cited by 3 publications

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Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype

Pathogenesis and Treatment of Prostate Cancer Bone Metastases: Targeting the Lethal Phenotype

Are Vaccines Making a Comeback in Non–Small-Cell Lung Cancer?

Paradigm Shifts in Cancer Vaccine Therapy

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