Dr. Weeks’ Comment: Is your oncologist STILL recommending chemotherapy and or radiation therapy? Of course she or he is. Why? NOT because it is clinically helpful or scientifically indicated. The only reason why your oncologist is not recommending corrective cancer care – targeting the cancer STEM cells- is because the standard of care must be adhered to until a committee of experts clarify that a better treatment is available. Simple as that. Your oncologist is not allowed to think for her or himself and offer corrective cancer care until the experts deem it valid. The trouble is, many “experts” are paid by industry to endorse (i.e. publish positive studies about) the standard of care. But the tide is shifting. Science has never required consensus or majority rule and todays experts are found to be as clueless as experts historically have been when paradigm shifts happen – the earth is found to not be flat after all, overuse of antibiotics is unhealthy, etc.
Now, here is yet another peer-reviewed scientific journal article urging oncologists to CHANGE their recommendations and to target the real culprit – the cancer STEM cells. Chemo and radiation kill cancer TUMOR cells (not a very dangerous cell, more like a by-stander at a riot) while they make cancer STEM cells “more numerous and more virulent”. Read the strident words below: “Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them.”
Citation: Oncogenesis (2015) 4, e177; doi:10.1038/oncsis.2015.35
Published online 30 November 2015
Targeting self-renewal pathways in cancer stem cells: clinical implications for cancer therapy
Extensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.
Cancer remains one of the deadliest diseases affecting large number of people worldwide every year. Even after profound cancer treatments, cancer relapse and drug resistance are reported. In the past decade, underlying cause discovered to be associated with tumor recurrence, metastasis and chemoresistance are a relatively small population of stem cells inhabiting each adult tissue called as the cancer stem cells (CSCs). These stem cells in the long run have the opportunity to accumulate the mutations required for malignant transformation owing to their unlimited division potential. These cells were first identified by Bonnet and Dick (1997)1 in acute myeloid leukemia and following their findings many other groups have identified these cells in various solid tumors of brain,2 breast,3 pancreas,4prostate5, 6 to name a few. CSCs display certain properties such as high expression of drug efflux transporters, abnormal cellular metabolism, deregulated SRPs, acquisition of epithelial-mesenchymal transition and extensive DNA-repair mechanisms.
Self-renewal is one of the important properties employed by the CSCs to maintain the proliferating capacities. As genetic and epigenetic changes might have a role in the unrestrained growth, invasion and acquired resistance in cancer cells, it is implicated that epigenesis may accord deregulation of self-renewal pathways (SRPs) in CSCs. There are number of signaling pathways functioning in the normal stem cells, which have assigned roles in the early embryogenesis-like cell proliferation, cell differentiation, cell fate, cell polarity and so on and are under strict regulation. In CSCs, these SRPs when deregulated lead to extensive cell proliferation and may be considered an early event in the process of carcinogenesis. Extensive experimental evidences have revealed Hedgehog (Hh), Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 (BMI1) pathways to be the key players in maintaining the proliferating capacity of CSCs and activated in most of the solid tumors.7 Among other signaling proteins such as phosphatase and tensin homolog,8 bone morphogenetic protein and transforming growth factor beta are also of specific interest as they too control self-renewal and cell differentiation in various tissues and are additionally implicated in tumorigenesis. Recent investigations of targeting the signaling pathways in CSCs have found to be of prime interest. This review focuses on several aspects of major SRPs, which are found to be upregulated in CSCs and certain novel strategies to target these pathways by nanodrug-delivery platforms for the prevention of tumor relapse and chemoresistance… for the rest of the article CLICK HERE