New Drug Application of Plinabulin (Response Letter from the FDA) for Prevention of Chemotherapy-Induced Neutropenia (CIN)...

 BeyondSpring Pharmaceuticals  announced the receipt of  a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) seeking approval of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN). The FDA issued the CRL to indicate that they have completed their review of the application and have determined that it cannot be approved in its present form.

 

The FDA’s CRL indicated that the results of the single registrational trial (106 Phase 3) was not sufficiently robust to demonstrate benefit and that a second well controlled trial would be required to satisfy the substantial evidence requirement to support the CIN indication.

“BeyondSpring strongly believes that plinabulin in combination with G-CSF has significant potential to raise the standard of care in CIN, a devastating side effect of chemotherapy,” said Dr. Lan Huang, BeyondSpring’s co-founder, chief executive officer and chairwoman. “The Company plans to request a meeting with the FDA and remains committed to its goal of bringing plinabulin to cancer patients in need globally.”

BeyondSpring remains confident in the efficacy and safety data for plinabulin in combination with G-CSF for the prevention of CIN. The Company expects to work closely with the FDA to consider the possible future clinical pathway for CIN, which may include a second study.

Plinabulin is the first drug candidate submitted for FDA approval that has the potential to work in the critical first week of chemotherapy treatment before G-CSF is effective, to prevent the onset and improve clinical outcomes of CIN.

Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected, NDA-stage asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation and priority review from both U.S. and China FDA for the CIN prevention indication. As a “pipeline in a drug,” plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

More

https://en.wikipedia.org/wiki/Plinabulin

Statin use alone or with metformin may increase survival in high-risk prostate cancer patients

In continuation of my update on metformin

Among high-risk prostate cancer patients - those with high PSA and Gleason scores of 8 or more - many will develop a difficult-to-treat disease. Preliminary research suggests that two commonly prescribed medications, cholesterol-lowering statins and the diabetes therapy metformin may have anticancer effects. However, it is unclear which of these two medications - commonly prescribed together -- contributes the most and whether they can impact high-risk prostate cancer. New research shows that statins, alone or with metformin, increase survival in men with high-risk prostate cancer.

"Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately," says senior author Grace Lu-Yao, PhD, associate director of Population Science at the Sidney Kimmel Cancer Center--Jefferson Health, one of only eight NCI-designated cancer centers nationwide with a prostate cancer program of excellence.

The study, published in Cancer Medicine on Feb 8th, looked at a number of statin therapies, and metformin, an anti-diabetic medication, in high-risk prostate cancer populations.

Using data from the Surveillance, Epidemiology and End Results (SEER-18) database linked with Medicare files, Dr. Lu-Yao and colleagues looked at patients diagnosed with cancer from 2007 through to 2011. Based on 12,700 patients, the researchers observed that statins alone or in combination with metformin was significantly associated with reduced mortality from all causes.

Dr. Lu-Yao and colleagues saw the highest median survival of 3.9 months in men who took both metformin and statins, 3.6 with statins alone and 3.1 years with metformin alone. The median survival for those who did not use either drug was also 3.1 years.

With respect to prostate mortality, metformin plus statin was associated with a 36% reduction in risk of death followed by statins alone. Those taking metformin alone were relatively rare, and there was no significant association with all-cause mortality."

Interestingly, the study revealed that men who took atorvastatin, pravastatin, or rosuvastatin - but not lovastatin - demonstrated a reduction in mortality compared with non-users, which is consistent with the findings from a recent population-based cohort study using Taiwan National Health Insurance Research Data. The Taiwanese research showed that these three statins are more effective at lowering triglycerides and low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol than other statins in patients with hypercholesterolemia.

Of the three statins studied, men on atorvastatin did have a longer median time to progression on androgen deprivation therapy compared to those who weren't treated with statins. "Although the exact mechanisms remain unknown, it is worth noting that atorvastatin exhibits a potent lipid-lowering effect per dose of any statin, and has the greatest bioavailability and one of the longest half-lives," says to Dr. Lu-Yao.

The data presented in the current study provide crucial insight for the design of future randomized clinical trials of statin for high-risk patients with prostate cancer. Based on the existing evidence, a well-designed clinical trial is warranted to investigate the roles of statins and combination statins/metformin to reduce the mortality cancer of the prostate.

"Our study showed that the effects were more pronounced in patients taking statins after the diagnosis of prostate cancer, 54% reduction in PCA mortality among patients with high-risk prostate cancer," says Lu-Yao. "This magnitude of reduction is comparable to the results of men treated with androgen signaling inhibitors." Statins are relatively inexpensive with good safety records. Further studies to understand the mechanisms of the observed association and its potential clinical utility are warranted.

https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.2862

Chemists synthesize garlic ingredient from readily available components

Fresh garlic extracts contain a variety of healthy organosulfur compounds, among which ajoene forms a major oil-extractable ingredient. Now, chemists in the United Kingdom have synthesized ajoene from readily available components for the first time. The results, which are published in the journal Angewandte Chemie, show that ajoene is accessible on a large scale with very few synthetic steps. Chemical synthesis of biologically active compounds is important for their further evaluation in medicinal research.

If garlic is cut or chewed, enzymes present in the damaged tissue start to degrade its main organosulfur metabolite, alliin. The first degradation product is allicin, which gives fresh garlic preparations their characteristic pungent odor. However, this molecule decomposes further into various, largely oil-soluble compounds, all characterized chemically as organosulfides or disulfides. A more stable decomposition product and main component in oil extracts is ajoene. This compound has similar health-promoting effects to allicin and it exhibits anticancer activity.

Although ajoene can be isolated from garlic extracts, chemical synthesis would have many advantages. Synthesized ajoene would allow the introduction of chemical modifications, a key provision in drug research. Therefore, Thomas Wirth and his group at Cardiff University in collaboration with the Welsh company Neem Biotech in the United Kingdom have now developed a fully synthetic approach based on simple, readily available components. The sequence starts with a simple dibromide and terminates with the oxidation of an organoselenium compound. Oxidative elimination of the selenium compound, the scientists noted, leads to the formation of the terminal carbon-carbon double bond characteristic for the ajoene molecule. At the same time, its sulfide moiety is oxidized to a sulfoxide, another characteristic chemical function in ajoene.

The biggest challenge in ajoene synthesis was minimizing the various side reactions typical for organosulfur compounds, Wirth and his team reported. Such side reactions profoundly decreased the yield in the biomimetic approach to ajoene, which started from allicin. But low yields turned out to be a problem in total synthesis as well. Therefore, the scientists explored several modifications in the reaction steps, but the most profound improvement, unexpectedly, came from scaling up the synthesis. On the 200-gram scale, the final oxidation yielded 56 percent of the product, the authors reported, which was twice as much as when working on the milligram scale.

The product was biologically active. Testing its activity against bacteria in a bioassay, Wirth and his group found that synthetic ajoene performed similarly to or even better than natural ajoene extracted from garlic. It inhibited biological communication called quorum sensing in Gram-negative bacteria, which may lead to biofilm formation. Inhibiting this could be a promising usage of ajoene, the authors suggested. And as total synthesis has now made this compound more easily accessible, its career in medicinal chemistry may be ready to take off.

Ref : https://newsroom.wiley.com/press-release/angewandte-chemie-international-edition/garlic-ingredient-lab-bench-short-total-synthe

Antimalarial drugs could find another use as cancer treatments, study says

Antimalarial drugs chloroquine and hydroxychloroquine could find another use as cancer treatments, according to a new clinical study published in ecancermedicalscience.

Researchers from the Repurposing Drugs in Oncology (ReDO) project, an international collaboration between the Anticancer Fund, Belgium, and USA-based GlobalCures, say there is evidence to include these drugs in further clinical investigations.

The authors are particularly excited about the potential for chloroquine and hydroxychloroquine as the evidence suggests they make tumor cells more sensitive to cancer treatment.
Chloroquine   Hydroxy chlroquine 

"What makes chloroquine and hydroxychloroquine so interesting is these multiple mechanisms of action", says Ciska Verbaanderd of the Anticancer Fund and the University of Leuven, Belgium, first author of the study."These antimalarial drugs act on both the level of cancer cells and the tumor microenvironment." Studying this has led to interesting scientific insights in tumor biology, such as the importance of autophagy, the tumor vasculature and the immune system."

"The results from the review lead us to believe that these antimalarial drugs could offer significant clinical benefit for certain cancer patients, especially in combination with standard anticancer treatments.This should be confirmed by additional clinical results."

Vikas P. Sukhatme MD ScD, co-founder of GlobalCures and one of the authors of this review, added "We look forward with much anticipation to the results of the 30 or so ongoing clinical studies that use chloroquine or hydroxychloroquine for cancer treatment."

The researchers' hope is that with the publication of this study, increased awareness of the potential applications will bring these medications out of the medicine cabinet - and into cancer care.

Previous papers from the ReDO project have explored how inexpensive, common drugs such as beta-blockers and anti-fungal remedies can be "repurposed" and used as part of cancer treatments.

Ref : http://ecancer.org/news/12864-antimalarial-drugs-could-support-existing-cancer-treatments-in-two-pronged-attack.php

Antimalarial drugs could find another use as cancer treatments, study says

Combination of diabetes and hypertension drugs can effectively treat cancer

In continuation of my update on metformin

  

Syrosingopine

  

                                                                        metformin

A combination of a diabetes medication and an antihypertensive drug can effectively combat cancer cells. The team of researchers led by Prof. Michael Hall at the Biozentrum of the University of Basel has also reported that specific cancer cells respond to this combination of drugs. The results of the study have now been published in "Science Advances".

Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. Besides its blood sugar lowering effect, it also displays anti-cancer properties. The usual therapeutic dose, however, is too low to effectively fight cancer. The research team led by Prof. Michael Hall, at the Biozentrum of the University of Basel, has now made an unexpected discovery: The antihypertensive drug syrosingopine potentiates the anti-cancer efficacy of metformin. Apparently, this drug combination drives cancer cells to programmed "suicide".

Drug cocktail kills tumor cells

At higher doses, the antidiabetic drug inhibits the growth of cancer cells but could also induce unwanted side effects. Therefore, the researchers screened over a thousand drugs for whether they can enhance the anticancer action of metformin. A favorite emerged from this screening: Syrosingopine, an antihypertensive drug. As the study shows, the cocktail of these two drugs is effective in a wide range of cancers.

"For example, in samples from leukemia patients, we demonstrated that almost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells", says the first author, Don Benjamin. "And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment."

Drugs block "juice" supply to cancer cells

In mice with malignant liver cancer, enlargement of the liver was reduced after the therapy. Also the number of tumor nodules was less - in some animals the tumors disappeared completely. A glance at the molecular processes in the tumor cells explains the drug combination's efficacy: Metformin lowers not only the blood glucose level, but also blocks the respiratory chain in the energy factories of the cell, the mitochondria. The antihypertensive drug syrosingopine inhibits, among other things, the degradation of sugars.

Thus, the drugs interrupt the vital processes which provide energy for the cell. Due to their increased metabolic activity and rapid growth, cancer cells have a particularly high energy consumption, which makes them extremely vulnerable when the energy supply is reduced.

Groundbreaking step towards clinical application

By testing a range of other compounds with the same mode of action, the scientists could demonstrate that the inhibition of the respiratory chain in the mitochondria is a key mechanism. These also reduced cancer cell growth in combination with the antihypertensive drug.

"We have been able to show that the two known drugs lead to more profound effects on cancer cell proliferation than each drug alone," explains Benjamin. "The data from this study support the development of combination approaches for the treatment of cancer patients." This study may have implications for future clinical application of combination scenarios targeting the energy needs of tumor cells.

Compounds extracted from parsley and dill seeds may help fight cancer

A team of Russian scientists from Moscow Institute of Physics and Technology (MIPT), the N. D. Zelinsky Institute of Organic Chemistry (RAS), the Institute of Developmental Biology (RAS), and the Institute of Cell Biophysics (RAS) proposed an efficient approach to a novel agents with anticancer activity. A synthesis of these compounds is based on compounds extracted from parsley and dill seeds. The results of the study have been published in the Journal of Natural Products.

"Both improvement of existing therapies and search for innovative approaches are essential components of a quest to treat cancer. Our combined team developed a simple method of producing glaziovianin A and its structural analogs, which inhibit the growth of human tumor cells, using feasible building blocks from nature. Furthermore, evaluation of these novel agents in vivo using our validated sea urchin embryo assays yielded several promising candidates selectively affecting tubulin dynamics" says MIPT professor Alexander Kiselev.

No growth for cancer cells

Currently, the main method of medical treatment for cancer is chemotherapy. The treatment uses antimitotics, which inhibit the growth of cancer cells by disrupting the process of cell division (mitosis).

Cancer cells divide much more frequently than normal cells and therefore they are more susceptible to the effects of antimitotics. For example, the number of melanoma cells doubles every 3 days, whereas the number of their healthy progenitors melanocytes increases by 15%, even when cell division is stimulated.

Microtubules play an important role in mitosis. They are composed of a protein called tubulin.

Antimitotics bind tubulin and affect microtubule dynamics disrupting cell cycle to result in arrested cell division and subsequent selective death.The study focused on the potent antimitotic agent glaziovianin A isolated from the leaves of the Brazilian tree Ateleia glazioviana Baill.

The reported synthesis of this agent is rather laborious and requires expensive precursors (substances that participate in reactions necessary for obtaining an end product) and catalysts (which accelerate chemical reactions). The authors proposed a novel and more efficient six-stage synthesis process (the normal process has nine stages) for glaziovianin A. Precursors for the process were derived from the seeds of common plants, namely parsley and dill.

In addition to glaziovianin A, a number of its structural analogs were synthesized in order to help find analogues with favorable antimitotic properties. The antitumor activity was tested via two independent methods using the sea urchin embryos and human cancer cells.

On sea urchins and cancer cells

The embryos of sea urchins were used to mimic actively dividing tumor cells dependent on tubulin dynamics. The scientists added test substances to an aqueous medium with the embryos and determined the concentrations at which the rate of division changes and when it comes to a complete stop. The lower the concentration, the greater the antimitotic activity the substance has. As the authors of the study established previously, when division is disrupted due to specific antitubulin activity of an agent, the embryos of sea urchins start spinning axially. Conveniently, this effect can be easily observed using a common light microscope.

Using the embryos, scientists are able to determine several important parameters essential for an anti-cancer molecule 'in one shot." These include a specific antimitotic effect, solubility, overall toxicity and biomembrane permeability.

To further confirm the antitumor effect of active molecules, they were studied with various human cancer cells, ex. lung carcinoma, melanoma, prostate, breast, colon, and ovarian cancers. The experiments showed that the test substances were effective at limiting the growth of melanoma cells, and non-toxic to healthy blood cells used as a control. Detailed structure-activity relationship studies in both assay systems converged on the parent glasiovianin A to be the most active anti-tubulin agent. Future plans include both optimization of the compound to improve its metabolic stability and solubility as well as human xenograft studies in mice to confirm anti-tumor activity and clinical development potential.

Compounds extracted from parsley and dill seeds may help fight cancer

Investigational drug abemaciclib shows durable clinical activity for variety of cancer types

In continuation of my  updates on palbociclib (Ibrance)  and letrozole

Bottom Line: The investigational anticancer therapeutic abemaciclib, which targets CDK4 and CDK6, showed durable clinical activity when given as continuous single-agent therapy to patients with a variety of cancer types, including breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, and melanoma, according to results from a phase I clinical trial.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research.

Senior authors: Amita Patnaik, MD, associate director of clinical research at South Texas Accelerated Research Therapeutics in San Antonio, Texas, and Geoffrey I. Shapiro, MD, PhD, director of the Early Drug Development Center at the Dana-Farber Cancer Institute in Boston.

Background: In February 2015, the U.S. Food and Drug Administration (FDA) approved the CDK4/6 inhibitor palbociclib (Ibrance) for use in combination with the aromatase inhibitor letrozole for treating postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer.

  letrozole  palbociclib

The oral CDK4/6 inhibitor abemaciclib is a very different molecule from palbociclib, with distinct attributes that contribute to its discrete therapeutic effects, in particular, its single-agent activity, according to Shapiro. For example, abemaciclib has greater selectivity for CDK4 compared with palbociclib, which may explain why it does not affect white blood cell counts as severely, allowing it to be taken on a continuous schedule without treatment holidays, he said. Abemaciclib also penetrates the central nervous system, whereas palbociclib does not, raising the possibility that it could be used to treat primary or metastatic brain tumors, he added.

 abemaciclib

How the Study Was Conducted and Results: Patnaik, Shapiro, and colleagues enrolled 225 patients with a variety of types of advanced cancer in the phase I clinical trial designed to evaluate the safety and preliminary efficacy of abemaciclib. In the dose escalation phase, the researchers determined that the maximum tolerated dose was 200 milligrams (mg) every 12 hours; the dose-limiting toxicity was grade 3 fatigue.

In the expansion phase, single-agent abemaciclib was administered to 47 patients with breast cancer, 68 with NSCLC, 17 with glioblastoma, 26 with melanoma, and 15 with colorectal cancer. Among these patients, the most common treatment-related adverse events were fatigue, diarrhea, nausea, vomiting, anorexia, weight loss, kidney dysfunction, and decreased red and white blood cell counts.

Radiographic responses were observed for some patients with breast cancer, NSCLC, and melanoma. Among the 36 patients with hormone receptor-positive breast cancer, 11 had a partial response, with four of the 11 responders having continued prior endocrine therapy, and an additional 18 patients had stable disease. Among the 68 patients with NSCLC, two had a partial response and 31 had stable disease; one patient who had a partial response and 12 who had stable disease were known to have KRAS-mutant NSCLC. Among the 26 patients with melanoma, one had a partial response and six had stable disease. Three of the 17 patients with glioblastoma had stable disease, with two of them continuing to receive treatment without disease progression for 19 and 23 cycles, respectively.

Author Comment: "These data show that abemaciclib is an oral drug that can be taken on a continuous schedule and achieve durable clinical activity against multiple tumors including breast and lung cancers," said Shapiro.

"The results of the trial supported the FDA decision to grant breakthrough therapy designation to abemaciclib (previously known as LY2835219) for patients with refractory hormone receptor-positive advanced or metastatic breast cancer," added Patnaik.

Limitations: Patnaik explained that because this study included 225 patients with different types of cancer, confirmatory clinical trials in specific patient populations are necessary to precisely define the role of abemaciclib in cancer care. Multiple clinical trials have already been initiated to evaluate abemaciclib as a treatment for certain groups of patients with breast cancer and NSCLC, as well as children with primary brain tumors and adults with brain metastases, she noted.

Novel combination of cancer drugs can have therapeutic impact on diffuse large B-cell lymphoma

In continuation of my update on carfilzomib, JQ1 and ABT 199

New research from Roswell Park Cancer Institute (RPCI) shows that promising cancer drugs used in combination can have significant therapeutic impact on a particularly aggressive subtype of diffuse large B-cell lymphoma (DH-DLBCL) in preclinical studies. The researchers will present their findings at the American Association for Cancer Research (AACR) Annual Meeting 2016, to be held April 16-20 in New Orleans.

Priyank Patel, MD, a fellow in the Department of Medicine at Roswell Park, is the first author and Francisco Hernandez-Ilizaliturri, MD, Clinical Chief of the Institute's Lymphoma/Myeloma Service, is the senior author of "Investigating novel targeted therapies for double hit diffuse large B-cell lymphoma (DH-DLBCL)" (abstract 3038), which will be presented on Tuesday, April 19, at 8 a.m. CDT.

Diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma, is an aggressive form of lymphoma. This research team reviewed a database of 650 patients with diffuse large B-cell lymphoma, identifying 36 patients whose tumors had two or more aberrant genes. Patients with mutations of the c-MYC, BCL2 and/or BCL6 genes — a subtype known as "double-hit lymphoma" — have especially have poor outcomes when treated with standard chemotherapy. The scientists evaluated the effectiveness of three novel anticancer drug candidates that targeted those proteins. In preclinical studies, the therapeutic agents ABT-199, JQ-1 and carfilzomib induced cell death in a dose- and time-dependent manner. Significant synergistic activity was observed when researchers combined ABT199 with carfilzomib and, to a lesser extent, with JQ1 in cancer cell lines.

"Increasing knowledge of genetics and molecular pathways has helped us identify a subgroup of patients who harbor aggressive aberrant gene mutations. Understanding the mechanisms of action and clarifying how these potential therapies work to inhibit cancer cell growth may result in improved outcomes for patients diagnosed with this aggressive type of lymphoma," says Dr. Hernandez-Ilizaliturri.

 Carfilzomib   JQ1  ABT-199

Novel combination of cancer drugs can have therapeutic impact on diffuse large B-cell lymphoma: New research from Roswell Park Cancer Institute shows that promising cancer drugs used in combination can have significant therapeutic impact on a particularly aggressive subtype of diffuse large B-cell lymphoma (DH-DLBCL) in preclinical studies. The researchers will present their findings at the American Association for Cancer Research (AACR) Annual Meeting 2016, to be held April 16-20 in New Orleans.

STA inks license and commercialisation agreement with PharmaMar for APLIDIN (plitidepsin)

Australian biopharmaceutical company Specialised Therapeutics Australia has struck an exclusive license and commercialisation agreement with European pharmaceutical partner company PharmaMar to market and distribute the novel oncology drug APLIDIN® (plitidepsin) in Australia and New Zealand.

Under the terms of the agreement, PharmaMar will receive an upfront payment, royalties and additional remunerations for regulatory and sales milestones achieved by APLIDIN® (plitidepsin).

PharmaMar will retain production rights and will supply the finished product to STA for exclusive commercial use in Australia and New Zealand.

APLIDIN® (plitidepsin) is PharmaMar´s second anticancer drug candidate obtained from a marine organism. This first in class drug is currently in development for the treatment of multiple myeloma and a type of T cell lymphoma. The company announced in June that patient recruitment of the international pivotal Phase III trial (ADMYRE) for APLIDIN® (plitidepsin) in refractory/relapsed multiple myeloma was successfully completed.

STA inks license and commercialisation agreement with PharmaMar for APLIDIN (plitidepsin)

This Little Known Chinese Herb Kills 12,000 Cancer Cells For Every Healthy Cell | Collective-Evolution

A little known Chinese herb might be eligible for the growing list of cancer killers via alternative methods of treatment. According to  studies published  in Life Sciences, Cancer Letters and Anticancer Drugs, artemesinin, a derivative of the wormwood plant commonly used in Chinese medicine, can kill off  cancer cells, and do it at a rate of 12,000 cancer cells for every healthy cell.

Henry Lai and his team of researchers from the University of Washington synthesized the compound, which uses a cancer cells appetite for iron to make them the target. The great thing about artemisinin is that alone it can selectively kill cancer cells while leaving normal cells unharmed.

“By itself, artemisinin is about 100 times more selective in killing cancer cells as opposed to normal cells. Artemisinin is 34,000 times more potent in killing the cancer cells as opposed to their normal cousins. So the tagging process appears to have greatly increased the potency of artemisinin’s cancer-killing properties.” – Henry Lai

Despite the compound being licensed to Holley Pharmaceuticals, it has yet to be used for cancer treatment in humans.

“We call it a Trojan horse because the cancer cell recognizes transferrin as a natural, harmless protein. So the cell picks up the compound without knowing that a bomb (artemisinin) is hidden inside.”  – Henry Lai

The wormwood extract was used many centuries ago in China for healing purposes. The treatment became lost over time and has now been rediscovered thanks to an ancient manuscript containing medical remedies. It kills 12,000 cancer cells for every healthy cell, which means it could be turned into a drug with minimal side effects.

“The compound is currently being licensed by the University of Washington to Artemisia Biomedical Inc., a company that Lai, Sasaki and Narendra Singh, UW associate professor of bioengineering, founded in Newcastle, Washington for development and commercialization. Human trials are at least several years away. Artemisinin is readily available, Sasaki said, and he hopes their compound can eventually be cheaply manufactured to help cancer patients in developing countries.”

This Little Known Chinese Herb Kills 12,000 Cancer Cells For Every Healthy Cell | Collective-Evolution

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

In continuation of my update on Ibrutinib

 

We know that, Ibrutinib   also known as PCI-32765 and marketed under the name Imbruvica) is an anticancer drug targeting B-cell malignancies. It was approved by the US FDA in November 2013 for the treatment of mantle cell lymphoma and in February 2014 for the treatment of chronic  lymphocytic leukemia  It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase (BTK)  Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson'sJanssen Pharmaceutical division for additional B-cell malignancies including diffuse large B-cell lymphoma and multiple myeloma

--------------------

Now.....

The most recent results from a clinical trial show that ibrutinib, a newly approved drug for Waldenstrom's Macroglobulinemia, continued to control the rare blood cancer, with 95 percent of patients surviving for two years, report investigators from Dana-Farber Cancer Institute.

The median overall response rate was 91 percent after a median of 19 months of treatment, and in 69 percent of patients the cancer had not worsened two years after beginning treatment. When the cancer did progress, it began at a median time of 9.6 months after the start of treatment. The results are reported in The New England Journal of Medicine.

An earlier analysis of data from this phase 2 multicenter study supported the Food and Drug Administration's approval in January of ibrutinib as the first and only treatment for Waldenstrom's, a rare form of lymphoma that affects about 1,500 people annually in the United States.

"These findings herald a new era for the treatment of Waldenstrom's Macroglobulinemia, and show how genome sequencing can lead to the discovery of cancer mutations that can be specifically targeted by new therapies," said first author Steven Treon, MD, PhD, director of the Bing Center for Waldenstrom's Macroglobulinemia at Dana-Farber.

Newly approved drug for rare blood cancer shows sustained benefit for 2 years

Itraconazole drug shows potential in cancer treatment

In continuation of my update on Itraconazole

Anti-fungal drug shows promise as potential new cancer treatment.A common anti-fungal treatment has joined the ranks of drugs that may be suitable for use in treating cancer, according to research from the Repurposing Drugs in Oncology (ReDO) project published in ecancermedicalscience.  

The ReDO project is an international collaboration of anticancer researchers dedicated to promoting the cause of common medicines which may represent an untapped source of novel therapies for cancer.

In partnership with ecancer, the ReDO project is publishing a series of papers on drugs that have enough clinical evidence to be taken to clinical trials.Itraconazole is a drug used to treat a broad range of fungal infections, including skin and nail infections.

It also has a lot of potential as a new cancer treatment, according to the ReDo project.

"Itraconazole shows potential in a number of areas with high unmet patient needs, particularly in non-small cell lung cancer and possibly in some rarer malignancies," says Pan Pantziarka, PhD, member of the ReDO project and the Anticancer Fund.

Itraconazole drug shows potential in cancer treatment

Chemical found in stinging nettles and ants could improve cancer drug

A cancer drug could be made 50 times more effective by a chemical found in stinging nettles and ants, new research finds. Researchers at the University of Warwick found that when the chemical, Sodium Formate, is used in combination with a metal-based cancer treatment it can greatly increase its ability to shut down cancer cells.

Developed by Warwick's Department of Chemistry, the drug, a compound of the metal ruthenium called JS07, is capable of exploiting a cancer cell's natural weaknesses and disrupts its energy generation mechanism.

Laboratory tests on ovarian cancer cells have shown that when used in combination with Sodium Formate JS07 is 50 times more effective than when acting alone. Derived from formic acid which is commonly found in a number of natural organisms including nettles and ants, Sodium Formate (E-237) is more commonly used as a food preservative.

The Warwick researchers developed a novel method for binding Sodium Formate with JS07 to form a more potent form of the drug. The researchers subsequently found that the potent form of JS07 acts as a catalyst when it interacts with a cancer cell's energy-generating mechanism. This interaction disrupts the mechanism, causing the cell's vital processes to cease functioning and for the cell to shut down.

Chemical found in stinging nettles and ants could improve cancer drug

Taiho Oncology announces acceptance of TAS-102 NDA for review by FDA

Taiho Oncology, Inc., a subsidiary of Taiho Pharmaceutical Co., Ltd. (Japan), today announced the New Drug Application (NDA) for TAS-102 (nonproprietary names: trifluridine and tipiracil hydrochloride), has been accepted for review by the U.S. Food and Drug Administration (FDA). TAS-102 is an oral combination investigational anticancer drug for the treatment of refractory metastatic colorectal cancer (mCRC).

TAS-102 is an investigational drug candidate for metastatic colorectal cancer. It is a combination of two active pharmaceutical ingredients: trifluridine, (see left structure)  

a nucleoside analog (see right structure), and tipiracil hydrochloride, a thymidine phosphorylase inhibitor. Tipiracil hydrochloride prevents rapid metabolism of trifluiridine, increasing the bioavailability of trifluiridine.

"The FDA's filing of the TAS-102 NDA represents a significant milestone for our company and underscores the need for new treatment options for patients with refractory metastatic colorectal cancer," said Eric Benn, Taiho Oncology's president and chief executive officer. "Today, we are one step closer to our ultimate goal of gaining regulatory approval for TAS-102 and making it available to patients in the USA with this serious medical condition. We look forward to working closely with the FDA during the NDA review."

Taiho Oncology announces acceptance of TAS-102 NDA for review by FDA

FL118 agent shows efficacy as personalized, targeted therapy for certain cancer tumors

A team led by Fengzhi Li, PhD, and Xinjiang Wang, PhD, of Roswell Park Cancer Institute (RPCI) has reported new findings regarding therapeutic targets of the novel anticancer agent FL118. Previous studies from these researchers have showed that FL118 induces cancer cell death, or apoptosis, by inhibiting expression of multiple cell-survival proteins (survivin, Mcl-1, XIAP or cIAP2). Study results published in the peer-reviewed American Association for Cancer Research journal Cancer Research  showed that FL118 can also activate   the p53 tumor-suppressor pathway in cancer cells, encouraging cell senescence,    or aging. In both processes, FL118 demonstrates potent antitumor efficacy,   suggesting additional applications as a personalized, targeted therapy for certain cancer tumors.

In a study of preclinical models of colorectal cancer, the researchers identified an underlying mechanism for the activation of p53 by FL118. The agent activates the p53 tumor-suppressor protein largely independent of ataxia telangiectasia mutated (ATM)-dependent DNA damage-mediated p53 activation. ATM-dependent activation of p53 is usually induced by many — if not all  types of DNA-damage drugs, including camptothecin compounds such as irinotecan and topotecan,  leading  the authors  to  conclude  that  FL118's mechanisms of action are distinct among camptothecin analogues.

"While FL118 is an analogue of irinotecan and topotecan, two FDA-approved cancer drugs that are also based on the naturally occurring compound camptothecin, our findings add further evidence that FL118 has novel mechanisms of action that may make it especially potent against solid tumors and especially effective as a well-tolerated, targeted therapy," said Dr. Li, an Associate Professor of Oncology in the Department of Pharmacology and Therapeutics.

FL118 agent shows efficacy as personalized, targeted therapy for certain cancer tumors

Cornerstone's CPI-613 drug candidate chosen as 2014 Top 10 Most Interesting Oncology Projects to Watch

We know that, CPI-613: CPI-613  is a racemic mixture of the enantiomers of a synthetic alpha-lipoic lipoic acid analogue with potential chemopreventive and antineoplastic activities. Although the exact mechanism of action is unknown, alpha-lipoic acid analogue CPI-613 has been shown to inhibit metabolic and regulatory processes required for cell growth in solid tumors. Both enantiomers in the racemic mixture exhibit antineoplastic activity. The mechanism-of-action of CPI-613 appears distinct from the current classes of anti-cancer agents used in the clinic. CPI-613 demonstrates both in vitro and in vivo anti-tumor activity.CPI-613 was known to strongly disrupt tumor mitochondrial metabolism. CPI-613 disruption of tumor mitochondrial metabolism is followed by efficient commitment to cell death by multiple, apparently redundant pathways, including apoptosis, in all tested cancer cell lines. Further, CPI-613 shows strong antitumor activity in vivo against human non-small cell lung and pancreatic cancers in xenograft models with low side-effect toxicity. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). (last updated: 10/30/2014)

Now...........

Cornerstone Pharmaceuticals, Inc., a development stage company and leader in the growing field of cancer metabolism-based therapeutics, today announced that its lead compound CPI-613 has been chosen by Informa and Kantar Health as one of the 2014 Top 10 Most Interesting Oncology Projects to Watch.

Steve Carchedi, Chief Executive Officer of Cornerstone Pharmaceuticals, will present at Informa’s Therapeutic Area Partnerships meeting, taking place November 19-21, 2014 at the Hyatt Regency in Boston. Mr. Carchedi’s presentation will occur at 11:00 a.m. on November 20 within Track 3 (Oncology).

During the presentation, Mr. Carchedi will discuss differentiators of Cornerstone’s lead Altered Energy Metabolism Directed (AEMD) drug candidate, CPI-613, which is a first-in-class anticancer compound designed to disrupt the altered energy-production pathways in cancer cells by targeting mitochondrial metabolism.

Cornerstone's CPI-613 drug candidate chosen as 2014 Top 10 Most Interesting Oncology Projects to Watch

New anticancer compound discovered

A team of research scientists from VTT Technical Research Centre of Finland, the University of Turku and the University of Eastern Finland has discovered a previously unknown Cent-1 molecule that kills cancer cells. Their research also shows that new cancer drug candidates can be identified faster and at lower cost by using computer-assisted and cell-based screening of compounds.

Ref: http://mct.aacrjournals.org/content/13/5/1054

New anticancer compound discovered 

Cancer treatment revolution potential with new drug

A new study at the University of Warwick, published today in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.

Called ZL105, the drug is a compound based on the precious metal iridium (organoiridium(III) complex [(η⁵-Cp^xbiph)Ir(phpy)(Cl)]). The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.

Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."

Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.

Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.

"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by
patients" argues Professor Sadler.

This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

Cancer treatment revolution potential with new drug