Breast and colon cancer represent the leading causes of
mortality in developed countries. The treatment options for these organ site
cancers differ depending on the status of hormone/growth factor receptors in
molecular subtypes that exhibit altered expression of oncogenes/tumor
suppressor genes and growth factormediated molecular pathways. Conventional
cytotoxic chemo-endocrine therapy traditionally includes the use of
anthracyclin, taxol, cisplatin, anti-estrogens, antifolates and DNA
anti-metabolites. Additionally, the use of molecular pathway-specific small
molecule inhibitors represents evidence-based targeted therapy. Long-term
conventional or targeted therapy using pharmacological agents is frequently
associated with systemic toxicity, acquired tumor resistance and the emergence
of drug-resistant cancer stem cells. These limitations are associated with the
progression of the therapyresistant disease.
Natural products such as dietary phytochemicals, their
respective bioactive agents, botanicals, nutraceuticals and nutritional herbs
are widely used in complementary and alternative medicine in women for
estrogen-related issues, osteoporosis and breast diseases. Unlike conventional
or targeted chemo-endocrine therapeutics, natural products, mainly due to their
low systemic toxicity, may not lead to acquired tumor resistance and therefore,
represent testable alternatives against therapy-resistant cancer.
These aspects emphasize a need to develop reliable
experimental approaches, and specific and sensitive biomarkers that facilitate
the identification of effective testable alternatives against therapy-resistant
cancer.
Models for drug-resistant stem cells have been developed and
characterized from the parental breast and colon carcinoma-derived cell lines,
as well as from the cell lines derived from genetically predisposed colon
cancer models. These stem cell models are characterized by the quantifiable
expression status of select stem cell-specific cellular and molecular markers.
Mechanistically distinct natural products have documented
growth-inhibitory effects on parental cell lines. Some of these agents also
exhibit stem cell targeted growth inhibitory efficacy.
Recognizing clinical evidence for the role of estrogens in
breast and colon cancer, future investigations include the development of tumor
organoid models of therapyresistant breast and colon cancer from female
patient-derived xenografts. These investigations support a scientifically
robust rationale to provide clinical translatability for patient-derived
preclinical data.
This chapter summarizes the evidence relevant to
experimental models systems, natural products and efficacy of lead compounds as
stem cell-targeted testable alternatives against breast and colon cancer.
Collectively, discussed evidence and its clinical relevance support the
hypothesis that natural products may benefit patients that are diagnosed for
therapy resistant cancers.
Keywords: Breast and colon cancer, Drug-resistant stem cells, Naturally occurring substances, Preclinical cellular models.
