Cancer Stem Cell Theory
Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. Cancer stem cells are therefore an underlying cause of tumor recurrence and metastasis. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. The majority of cancer drugs, while killing the bulk of tumor cells, fail to induce durable clinical responses because stem cells are able to develop a resistance to treatment over time. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.
"The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term" (1). Another important implication in the stem cell theory is that it is the cancer stem cells that give rise to metastases and that stem cells provide a resevoir of cells which are resistant to chemotherapy and allow for the relapse of cancer.
According to the cancer stem cell theory tumours grow like normal tissues of the body, with stem cells at the starting point of an organised system that produces new cells to make a tissue grow.
The Role of FGF In Cancer Stem Cells
Nearly every cell in the body expresses the FGF protein, but there are 22 different types. In humans, 22 members of the FGF family have been identified, all of which are structurally related signaling molecules. The mammalian fibroblast growth factor receptor family has 4 members, FGFR1, FGFR2, FGFR3, and FGFR4.
FGF signalling mediated by FGFR follows a classic receptor tyrosine kinase signalling pathway and its deregulation at various points of its cascade could result in malignancy.
FGFR inhibitors
Although targeting FGF signalling as a cancer therapeutic target has lagged behind that of other receptor tyrosine kinases, there is now substantial evidence for the importance of FGF signalling in the pathogenesis of diverse tumour types. " Dovitinib, Ki23057, ponatinib, and AZD4547 are orally bioavailable FGFR inhibitors, which have demonstrated striking effects in preclinical model experiments. Dovitinib, ponatinib, and AZD4547 are currently in clinical trial as anticancer drugs. Because there are multiple mechanisms of actions for FGFR inhibitors to overcome drug resistance, FGFR-targeted therapy is a promising strategy for the treatment of refractory cancer." (6)
Readings and References
1-The Stem Cell Theory of Cancer
2-Anti-Cancer Agents in Medicinal Chemistry
3- Cancer -- a disease of stem cells?
4- Can stem cells cause and cure cancer?
6- FGF receptors: cancer biology and therapeutics.
7- Mechanisms of FGFR-mediated carcinogenesis