Dr. Weeks’ Comment: When lecturing to doctors on Corrective Cancer Care, I typically quote Thomas Pychon in Gravity’s Rainbow when he cautions “If you can get people to ask the wrong question, the answer doesn’t matter.” So, if I am a cancer patient, what is the wrong question? It is a mis-direct question like: “How can I kill cancer tumor cells?” (Remember: chemotherapy and radiation therapy kill only cancer TUMOR cells while making the lethal cancer STEM cells “more numerous and more virulent”. Researches are only now (NATURE December 2014!) focusing on what doctors offering Corrective Cancer Care have know for almost a decade. That chemotherapy HARMS YOU because it stimulates the lethal cancer STEM cells.
“….Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to repopulate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation….” (read whole article here)
So what is the RIGHT question? The right question for your oncologist is “How can I kill my cancer STEM cells – the only cells which metastasize – and the really lethal cells?” Answer: anti-inflammatory agents the most valuable of which is eating anti-inflammatory seeds.
P-cadherin is a classical cell-to-cell adhesion molecule with a homeostatic function in several normal tissues. However, its behaviour in the malignant setting is notably dependent on the cellular context.
In some tumour models, such as melanoma and oral squamous cell carcinoma, P-cadherin acts as a tumour suppressor, since its absence is associated with a more aggressive cancer cell phenotype; nevertheless, the overexpression of this molecule is linked to significant tumour promoting effects in the breast, ovarian, prostate, endometrial, skin, gastric, pancreas and colon neoplasms. Herein, we review the role of P-cadherin in cancer cell invasion, as well as in loco-regional and distant metastatic dissemination.
We focus in P-cadherin signalling pathways that are activated to induce invasion and metastasis, as well as cancer stem cell properties. The signalling network downstream of P-cadherin is notably dependent on the cellular and tissue context and includes the activation of integrin molecules, receptor tyrosine kinases, small molecule GTPases, EMT transcription factors, and crosstalk with other cadherin family members.
As new oncogenic molecular pathways mediated by P-cadherin are uncovered, putative therapeutic options can be tested, which will allow for the targeting of invasion or metastatic disease, depending on the tumour model.
Credits/Source: Molecular Cancer 2015, 14:178