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Cancer metastasis: a search for therapeutic inhibition
C J Dimitroff1, A Sharma, R J Bernacki
1Department of Pharmacology and Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York, USA.
Abstract:
Failure of cancer treatment is often due to the growth of secondary, metastatic lesions in distant organs. Because initiation of metastasis is an early event in malignancy, patients often present not only with a primary tumor but also with occult metastases. Treatment of these metastases requires aggressive, systemic chemotherapy, since surgical removal of all metastatic foci is normally not feasible. However, drug toxicity caused by many of the currently used anticancer agents often limits chemotherapeutic approaches to malignant disease. In contrast, the development and use of novel cytostatic, antimetastatic agents could be less toxic and more applicable for long-term treatment in combating latent and/or residual disease. Practical intervention with such nontoxic agents has been envisioned as maintenance therapy after cytoreduction of a tumor or as a prophylactic treatment after the removal of a precancerous tumor exhibiting a genetic predisposition to a carcinomatous state. In this review, we discuss targets of the metastatic cell that may be potentially exploitable with chemotherapy, and present the current status of several novel, antimetastatic agents. Clinical evaluation of such agents will require new and appropriate clinical models for evaluating their antimetastatic efficacy. The recent successes achieved with certain proteinase inhibitors for the treatment of cancer are paving the way for the development of other therapeutic agents of this type, aimed at unique biochemical pathways associated with oncogenic behavior.
Insights
Novel antimetastatic agents offer a less toxic, more effective approach to treating cancer metastasis. These agents target metastatic cells, potentially serving as maintenance or prophylactic therapy for latent disease.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Cancer treatment failure is often linked to the development of secondary metastatic lesions.
- Metastasis initiation is an early event, frequently resulting in patients presenting with both primary tumors and occult metastases.
- Current systemic chemotherapy for metastases faces limitations due to drug toxicity.
Purpose of the Study:
- To review potential targets within metastatic cells for novel chemotherapeutic strategies.
- To present the current status of novel antimetastatic agents.
- To discuss the potential of less toxic, cytostatic agents for long-term treatment of latent or residual cancer disease.
Main Methods:
- Review of current literature on cancer metastasis and therapeutic targets.
- Analysis of novel antimetastatic agents and their mechanisms of action.
- Discussion of clinical evaluation models for antimetastatic efficacy.
Main Results:
- Novel cytostatic, antimetastatic agents show promise for less toxic, long-term treatment.
- Exploitable targets in metastatic cells are being identified for chemotherapy.
- Successes in proteinase inhibitors pave the way for new therapeutic agents targeting oncogenic pathways.
Conclusions:
- Antimetastatic agents offer a promising alternative to conventional chemotherapy, particularly for combating residual or latent disease.
- Development of novel agents targeting specific metastatic cell pathways is crucial.
- New clinical models are needed to effectively evaluate the efficacy of these emerging antimetastatic therapies.