Introduction: What they say
A study from the Laboratory of Systems Pharmacology (at the Blavatnik Institute), Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; and Termeer Center for Targeted Therapies, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA shows that “Multiomics Profiling Establishes the Polypharmacology of FDA-Approved CDK4/6 Inhibitors and the Potential for Differential Clinical Activity.” This research paper was published, in the 6 June 2019 issue of the journal “Cell Chem Biol.”, by Prof. Peter Sorger, PhD., (Head of the Harvard Program in Therapeutic Sciences (HiTS) and Director of its Laboratory of Systems Pharmacology.), Prof. Dejan Juric (Director of the Termeer Center), Dr. Mark Hafner, Dr. Caitlin Mills 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 metastatic breast cancer and in other advanced metastatic cancers: A pharmaceutical mixture encompassing Abemaciclib, Metformin and probiotic Lactobacillus rhamnosus increases the expression of tumor suppressor genes, such as TPM1 and CADM1/2, p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls metastatic breast cancer progression, via up-regulation of its target gene, 1/September/2019, 1.55 pm
The Significance of the study to Public health relevance:
First, given that: (i) each year nearly 14 million people–more than 2 50,000 patients are diagnosed with breast cancer ever year in the US– 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?
Prof. Sorger‘s research team has recently shown that treating advanced metastatic breast cancers (Hormone receptor positive (HR+)/Epidermal growth factor receptor negative (HER2-) with Abemaciclib (a CDK4/CDK6 inhibitor) : (1) inhibits other cyclin dependent kinase (CDK)’s, such as CDK2/cyclin A/E-demonstrated to be involved in resistance to CDK4/6 inhibition-and CDK1/cyclin B (and hence, it may function as a pan-CDK inhibitor); and (2) the overall anti-tumor response; and cytotoxic response was much greater when compared with other anti-metastatic breast cancer drugs, such as Palbociclib (developed by Pfizer), and Ribociclib (developed by Novartis), suggesting that selective pan CDK inhibitor Abemaciclib is an effective treatment regimen for hormone receptor positive (HR+)/Epidermal growth factor receptor negative (HER2-) advanced metastatic breast cancer patients. However, the molecular mechanism of action of Abemaciclib in stalling the progression of advanced metastatic breast cancer remains largely unknown. Abemaciclib, whose brand name is Verzenio(marketed by Eli Lilly company), has been shown to be sold for $171.9 million in the first nine months of 2018. And, its sales projections reveal that it may reach $2.17 bn in 2024.
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 breast 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 Abemaciclib (trade name: Verzenio) and Metformin (AM), 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 TPM1 and CADM1/2; (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 Abemaciclib can be increased by treating cancer patients with probiotic Lactobacillus rhamnosus (1.0×103 CFU/ml).
Thus, a pharmacological formulation encompassing “Abemaciclib, and Metformin or their analogs/functional equivalents” either alone or in combination with other known anti-cancer/metabolic drugs, or probiotics enriched with anti-cancer activity, such as Lactobacillus rhamnosus,” may be used to inhibit the progression of advanced cancers, including metastatic breast cancer, and thereby 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 Abemaciclib increase the expression of tumor/metastatic suppressors TPM1 and CADM1/2?
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
For purchase and payment details, you may reach us at firstname.lastname@example.org
Web: http://genomediscovery.org or http://newbioideas.com/
Citation: Boominathan, L., Probiotic-based Chemotherapy (PCT) targeting cancer stem cells and immune-inhibitory receptors in metastatic breast cancer and in other advanced metastatic cancers: A pharmaceutical mixture encompassing Abemaciclib, Metformin and probiotic Lactobacillus rhamnosus increases the expression of tumor suppressor genes, such as TPM1 and CADM1/2, p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls metastatic breast cancer progression, via up-regulation of its target gene, 1/September/2019, 1.55 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org
Courtesy: When you cite, Kindly drop us a line at email@example.com