Introduction: What they say
A study from the the Division of Hematology, Department of Internal Medicine, Ohio State University, and the Department of Veterinary Biosciences, College of Veterinary Medicine – both in Columbus; UC Irvine Health Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange; University of Oxford, Oxford, NHS Foundation Trust, King’s College Hospital, London, and the Department of Haematology, St. James’s University Hospital, Leeds- all in the United Kingdom; Northwest Medical Specialties, Tacoma, and the Swedish Cancer Institute, Seattle – both in Washington; the Department of Leukemia, Division of Cancer Medicine, University of Texas, and M.D. Anderson Cancer Center – both in Houston; the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Huntsman Cancer Institute, University of Utah, Salt Lake City; Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milan; Hofstra North Shore-LIJ School of Medicine, Chronic Lymphocytic Leukemia Research and Treatment Center, Lake Success, and the Department of Pathology and Cell Biology, Columbia University Medical Center, and New York-Presbyterian/Weill Cornell Medical Center, New York- all in New York; and Acerta Pharma, Oss, the Netherlands shows the role of Acalabrutinib in controlling the progression of Relapsed Chronic Lymphocytic Leukemia. This research paper was published, in the 7 December 2015 issue of the journal “N Engl J Med. 2019 (NEJM)” [One of the best research journals in Medical Sciences with an I.F of 78 plus], by Dr. Furman RR., M.D., (Director of CLL Research center), Dr. Byrd JC., M.D., and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, the Director-cum-chief Scientist of GBMD, reports that: Probiotic-based Chemotherapy (PCT) targeting cancer stem cells and immune-inhibitory receptors in relapsed chronic lymphocytic leukemia (CLL) and in advanced metastatic cancers: A pharmaceutical mixture encompassing Acalabrutinib, and probiotic Lactobacillus rhamnosus increases the expression of tumor suppressor genes, such as PPP2R2A, HDAC8, p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls CLL progression, via up-regulation of its target gene
The Significance of the study to Public health relevance:
First, given that: (i) each year nearly 14 million people are diagnosed with cancer globally, and little more than half of them will die due to lack of curative treatment available at present; (ii) cancer deaths globally are expected to be doubled by 2030; and (iii) cancer causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (iii) a side-effect-free natural product-based anticancer drugs that target cancer stem cells; and (iv) a way to effectively treat and prevent metastatic progression and relapse of ovarian cancers.
Second, given that: (1) cancer suppressor p53 is mutated in more than 50% of human cancers of different tissue origin; (2) p53 pathway is altered in about 80% of tumors; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in mutant p53-overexpressing tumors; (4) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (5) cancer causes the considerable economic loss worldwide, there is an urgent need to find a way to effectively treat and stall metastatic progression and relapse of mutant p53-overexpressing human cancers.
What is known?
Dr. Furman MD’s research team has recently shown that treating relapsed chronic lymphocytic leukemia (CLL) patients with Acalabrutinib (a second- generation, more selective, irreversible inhibitor of Bruton’s tyrosine kinase (BTK) : (1) the overall response rate was 95% (total number of patients: 61; and Dose: 100 to 400 mg once daily ); (2) the overall response rate was 100% in patients with chromosome 17p13.1 deletion; and (3) resulting in no adverse side effects compared with ibrutinib, suggesting that selective BTK inhibitor Acalabrutinib is an effective treatment regimen for elderly patients (62+ years of age) with relapsed CLL. However, the molecular mechanism of action of Acalabrutinib in stalling the progression of CLL remains largely unknown.
From research findings to therapeutic opportunity :
(i) Therapeutic strategy:
This study suggests a therapeutic strategy for stalling the progression of p53-deficient/deleted or mutant-p53 expressing metastatic cancers. By activating tumor suppressor p53’s unmutated “homologous protein such as TAp73/p63” in p53-deficient or mutant-p53 expressing metastatic cancer cells, one can stall their progression.
(ii) Research findings: This study presented here suggests, for the first time, that a pharmacological formulation encompassing Acalabrutinib, by increasing the expression of its target genes, it may: (i) decrease the expression of a number of oncogenes and DNA repair proteins; (ii) increase the expression of tumor/metastasis suppressor genes, such as PPP2R2A, & HDAC8; (iii) increase the expression of a number of other tumor suppressor genes, including p53/TA-p73/p63, and their target genes, INKa, p19ARF and others (Figure 1);(iv) activate tumor/metastasis suppressor network; (v) inhibit immunosuppressive/immune-inhibitory receptors/ molecules; (vi) inhibit the activity and proliferation of cancer stem cells; (vii) inhibit tumor growth; and (viii) promote survival (Figures 1-4). Further, the efficacy of Acalabrutinib can be increased by treating cancer patients with probiotic Lactobacillus rhamnosus (1.0×103 CFU/ml).
Thus, a pharmacological formulation encompassing “Acalabrutinib or its analogs” either alone or in combination with other known anticancer/metabolic drugs, or probiotics enriched with anti-cancer activity, such as Lactobacillus rhamnosus,” may be used to inhibit the progression of advanced cancers, including CLL, and promote disease-free survival (Figure 3-4).
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Amount: $1, 500#
Undisclosed mechanistic information: How does a pharmacological formulation encompassing Acalabrutinib increase the expression of tumor/metastatic suppressors PPP2R2A, and HDAC8 ?
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Citation: Boominathan, L., Probiotic-based Chemotherapy (PCT) targeting cancer stem cells and immune-inhibitory receptors in relapsed chronic lymphocytic leukemia (CLL) and in advanced metastatic cancers: A pharmaceutical mixture encompassing Acalabrutinib, and probiotic Lactobacillus rhamnosus increases the expression of tumor suppressor genes, such as PPP2R2A, HDAC8, p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls CLL progression, via up-regulation of its target gene, 30/August/2019, 10.22 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org
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