As Einstein used to say, one of the proofs of insanity is to continue doing the same thing and expecting different results. In this realm or theatre of the Absurd, researchers from Albert Einstein College of Medicine of Yeshiva University have published a study that links chemotherapy to the spread of cancer and aggressive new tumors. Thereafter, the researchers proposed inhibitors thereto, instead of abandoning the chemo model thereof. In this blog-article, I will first examine the purported “new” findings of this study, (Section A) and in a second section, I will look at Conventional Oncology’s response to this discovery (Section B) and thenceforth, in the Discussion section, I will respectfully suggest that these findings are not new and just the continuation of the application of an absurd yet lucrative conventional oncology paradigm that spreads malignancy under the disguise of “tumor shrinkage” while amassing huge cash-flows. (Section Discussion)
One of the classical standards of care for many solid tumors is to bestow upon the cancer patient a blast of chemo in order the shrink the tumor. Thereafter, the oncological surgeons can rip open the skin and remove the reduced tumor and tell the patient “we got it all”, “clear margins” and the big one, “NED” (no evidence of disease), all of which tend to misleading, if only because the circulatory cancer stem cells, inter alia, are spurred to proliferate and get stronger when they are under chemo and knife attack.
Now, with this new piece of oncology study that comes from the Mainstream, from conventional oncology, we have more evidence that this approach is absurd as cytotoxic chemotherapy promotes the expression of astute malignancy defense systems that end up strengthening cancer stem cells and increasing proliferation and death. I already drafted multiple articles on this including on the fact that there has never been any credible study showing a causative relationship between the shrinkage of a tumor and survivability. A correlation, yes, but no causation. Ralph Moss, recipient of the Cancer Control Convention, has also written about this decades ago in his booklet on chemotherapy.
In this perspective then, Dr George Karagiannis, of the Albert Einstein College of Medicine of Yeshiva University, in New York, unmasked part of this above-mentioned mechanisms. What he empirically found was that the number of metastatic doorways was increased in patients receiving two common chemotherapy drugs.
Top: An image showing ‘doorways’ opening in blood vessels which allow tumours to spread: Credit: George Kragiannis
The Einstein University Professor also discovered that in mice, breast cancer chemotherapy increased the number of cancer cells circulating the body and in the lungs. This aspect we have already known for over one decade, that chemo as well as radiation spur cancer stem cells to migrate to distant tissues so that they can better express their evolutionary metastatic programmed task of subduing the human host and-or reducing predatory human population growth.
Proposed Conventional Solutions
The Conventional Oncology Models Adapts with more of the same
Dr Karagiannis, a conventionally trained oncologist, proposed two ways to get around this newly perceived challenged. First, the New York Professor proposes to obtain a small amount of tumour tissue after a few doses of preoperative chemotherapy to ascertain cancer’s metastatic potential. By obtaining via biopsy a piece of the tumor tissue and submitting its cancer cells to chemo to confirm if its metastatic doorways are opening, the Professor would know if it makes sense to give chemo after the surgery.
“If we observe that the markers scores are increased we would recommend discontinuing chemo and having surgery first, followed by post-operative chemo. We are currently planning more extensive trials to address the issue”. (Source)
As for proliferation, the researchers also determined that a drug called rebastinib can interfere with TMEM activity and help overcome the increased risk of cancer cell dissemination.
Discussion & Tentative Conclusion
Tumor microenvironment of metastasis & Common Sense
These Researchers unequivocably confirmed that chemo increases the chance of cancer cells migrating to other parts of the body. Many are given chemotherapy before surgery, but the new research suggests that, although it shrinks tumours in the short term, it can also trigger the spread of cancer cells around the body. So far, the best explanation is that chemo switches on a repair mechanism in the body which ultimately allows tumours to grow back stronger. It also increases the number of ‘doorways’ on blood vessels which allow cancer to spread throughout the body. These possible mechanisms ware ni addition to other proliferative mechanisms, to the Pump and from progenitor stem cells to bacterial intervention and more.
By studying the process of intravasation or entry of cells into the vasculature, Karagiannis et al. discovered that, in addition to killing tumor cells, the researchers found that chemotherapy treatment can also increase intravasation. Groups of cells collectively known as tumor microenvironment of metastasis (TMEM) can serve as gateways for tumor cells entering the vasculature, and the authors discovered that several types of chemotherapy can increase the amounts of TMEM complexes and circulating tumor cells in the bloodstream.
Pr. Joubert (ACRI director)
Reference and Precision Notes
“Breast cancer cells disseminate through TIE2/MENACalc/MENAINV-dependent cancer cell intravasation sites, called tumor microenvironment of metastasis (TMEM), which are clinically validated as prognostic markers of metastasis in breast cancer patients. Using fixed tissue and intravital imaging of a PyMT murine model and patient-derived xenografts, we show that chemotherapy increases the density and activity of TMEM sites and Mena expression and promotes distant metastasis. Moreover, in the residual breast cancers of patients treated with neoadjuvant paclitaxel after doxorubicin plus cyclophosphamide, TMEM score and its mechanistically connected MENAINV isoform expression pattern were both increased, suggesting that chemotherapy, despite decreasing tumor size, increases the risk of metastatic dissemination. Chemotherapy-induced TMEM activity and cancer cell dissemination were reversed by either administration of the TIE2 inhibitor rebastinib or knockdown of the MENA gene. Our results indicate that TMEM score increases and MENA isoform expression pattern changes with chemotherapy and can be used in predicting prometastatic changes in response to chemotherapy. Furthermore, inhibitors of TMEM function may improve clinical benefits of chemotherapy in the neoadjuvant setting or in metastatic disease”. (Source)
(1). The study was published in the journal Science Translational Medicine.
Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism
George S. Karagiannis1,2,*, Jessica M. Pastoriza1,3, Yarong Wang1,2,4, Allison S. Harney1,2,4,5, David Entenberg1,2,4, Jeanine Pignatelli1, Ved P. Sharma1,4, Emily A. Xue1, Esther Cheng6, Timothy M. D’Alfonso6, Joan G. Jones1,2,7,8, Jesus Anampa9, Thomas E. Rohan8, Joseph A. Sparano9, John S. Condeelis1,2,4,* and Maja H. Oktay1,4,7,*
Science Translational Medicine 05 Jul 2017: Vol. 9, Issue 397, eaan0026
This article has a correction. Is corrected by – July 19, 2017
In the manuscript “Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism,” there were errors in the data in Fig. 3I and Fig. 8B, as well as a P value and an R2 value in the subsection of the results titled “Paclitaxel promotes the expression of invasive isoforms of Mena in breast tumors.” The full text and PDF have been corrected. These corrections do not change the conclusions of the paper.
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