Cancer prevention and treatment using combination therapy with natural compounds

ABSTRACT

Introduction: Naturally occurring compounds play an essential role in the prevention and treatment of various cancers. There are more than 100 plant and animal based natural compounds currently in clinical use.

Areas covered: 1) The importance of natural products combinations in the prevention and treatment of cancer, 2) the need to maximize efficacy while minimizing side effects when using natural product combinations, and 3) specifics related to plant and animal derived natural products, as well as agents derived from natural products. Therapies using natural compounds that have been investigated, their rationale, mechanism of action and findings are reviewed. When the data warrant it, combined interventions that appear to increase efficacy (compared with monotherapy) while minimizing toxicity have been highlighted. Pubmed was used to search for relevant publications.

Expert opinion: Combination therapy with natural compounds has the potential to be more effective than single agent therapy. Similar to pharmacologic agents, the goal is to maximize efficacy while mimimizing potential side effects. There is an increasing research focus on the development of agents derived from natural products, with notable successes already achieved from the effort.

KEYWORDS:

• Cancer prevention
• cancer treatment
• natural compounds
• combination therapy

Article highlights

• Combination therapy to prevent or treat cancer, whether the agents used are natural or pharmacologic, has the potential to be more effective than single agent therapy.

• When using combination therapy, interactions may be beneficial (additive or synergistic), neutral or harmful (by increasing toxicity and/or decreasing efficacy).

• Both plant- and animal-derived natural compounds have demonstrated efficacy in cancer.

• The vast majority of reports to date on the efficacy of combination therapy that includes natural compounds to treat or prevent cancer have taken place in cell culture or animals.

• A limitation to progress in the use of natural compounds has been our lack of understanding of their mechanism(s) of action.

• There are extensive ongoing federal and commercial efforts to translate natural products into effective chemopreventive and chemotherapeutic agents.

• Most natural compounds are consumed as food, rather than as a single agent. Concentrations of the presumed active ingredient may vary in the food depending on climate conditions, and other compounds may influence efficacy. These factors need to be considered and variability minimized when human efficacy studies are conducted.

• Since natural compounds are generally found not as a single compound but rather as a plant or animal component, both identifying the active agent and determining the optimal dose are more difficult than with a manmade compound. Moreover, it is often difficult or impossible to know whether a combination of chemicals in a given food is required to achieve optimal anticancer activity. Better ways to address these challenges are needed.

• Natural products are not necessarily safer than manmade products. Toxicity assessment is critical to the development of natural products, whether evaluating single agents or agents used in combination.

• Agents derived from natural products are an area of increasing interest, with notable successes thus far, including in some instances approval from the FDA for the agent to be used to treat certain form(s) of cancer.

• When conducting human studies of a natural compound present in food, it may be worth comparing the pure compound to a similar concentration in the food to determine which mode of consumption optimizes efficacy.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.