ReviewFood-based natural products for cancer management: Is the whole greater than the sum of the parts?
Introduction
The global map of cancer prevalence is rapidly changing. While the western world is witnessing a decrease in most cancer-related mortality, incidence and mortality continue to rise rapidly in developing and underdeveloped countries. The International Agency for Research on Cancer reported that 64.9% of cancer-deaths in 2012 occurred in less developed regions of the world [1]. About 97% of growth in world population in 2012 was also attributed to that of developing nations. Considering this unexpected growth, and higher life expectancies, it is projected that new cancer cases will dramatically increase from 14.1 million in 2012–19.3 million by 2025 [1], [2]. This crippling global cancer scenario raises immense concerns regarding accessibility to treatment due to excessive cost of modern cancer care in general and limited access to exorbitant therapeutics in developing countries in particular. Further, increased survival is also accompanied by increased healthcare costs to monitor many recurrent cancers. These devastating facts underscore the need for economical and novel interventions that may have a larger global reach. The ability to use naturally occurring materials to manage cancer is an appealing alternative to overcome these alarming statistics. Given the large numbers of starting materials in nature, the various isolated compounds, complexities of different cancers and the recapitulation of preclinical tumor models make it very clear that we have to ensure that the most commonly tested natural whole extract and/or their isolated compounds are fully and scientifically vetted to facilitate their use for cancer management. Chemoprevention in general and prevention with phytochemicals has been widely studied in 4 of the most common cancers including lung, colon, breast and prostate. In this review we focus largely on prostate cancer. Cell culture studies that reveal mechanistic aspects of the effects of these compounds and their parent extracts are also presented. As discussed here validation of these molecular mechanisms may facilitate their use as surrogate markers of efficacy in clinical trials.
Section snippets
Whole vs. isolated compound entities
An array of natural foods including tomatoes, grapes, green tea, soybeans, milk thistle, broccoli, pomegranate, black raspberries, and isolated compounds from them have been explored in various preclinical and clinical settings for their anti-cancer potential [3], [4], [5], [6], [7], [8]. Clearly patients in developed countries are willing to explore botanicals/natural products as alternatives to manage cancers. In a study to assess interest in participating in a botanical chemoprevention trial
Natural products as adjuvants in cancer therapy
The potential clinical benefits of phytochemicals from foods are becoming increasingly evident. The lack of systemic toxicity of these extracts makes them particularly promising as adjuvants in cancer therapy. The combination of natural products with the standard of care treatment is an emerging area of cancer therapeutics with a multitude of benefits such as dose reduction, synergistic effect and delay in development of drug-resistance. Along these lines, a recent meta-analysis of 29 different
Challenges in clinical development of natural products
From the examples of studies listed above it is clear that we are far from concluding whether the whole natural extract or its most prominent chemical constituent should be the candidate anti-cancer agent for clinical testing. The examples above also highlight shortcomings such as lack of standard design including but not limited to duration of treatment, inclusion of proper control arms, choice of cancer stage, outcome measures and the nature of the natural product. For example from the tomato
Future directions
The rationale adopted by scientists at the US National Cancer Institute in the 1950s to identify drugs from nature was based on the premise of ‘one active compound-one disease treatment’. This approach was driven by the state of the scientific understanding of cancer cell biology at that time. Further, the concept of synergy between different components within the whole botanical to affect cancer cell functions was not recognized. A better understanding of how cancer cells are wired (Fig. 3)
Acknowledgements
Supported by funds from AT007448 and CPRITRP150166 (APK) CA149516 (RG) and by the CTRC at UT Health Science Center San Antonio (UTHSCSA) through NCI support grant #2P30 CA 054174-17.
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