New drug limits cancer spreading

A research team that recently invented a drug to stop blood vessels from forming a treatment-resistant barrier around some cancers has now discovered the drug can be used to prevent cancer from spreading.

"We originally developed the drug to overcome a problem in some cancers that grow a chaotic barrier of blood vessels in the tumor which prevents the body's immune cells and treatments like chemotherapy entering the tumor," said Professor Ruth Ganss Co-Head of the Cancer and Cell Biology Division at Perth's Harry Perkins Institute of Medical Research.

"The drug also sets-up lymph-node-like structures within the cancer to draw in a patient's immune system and greatly enhance a patient's own capacity to shrink the cancer.

"What we've since discovered is that by 'normalizing' blood vessels the drug also stops cancer spreading because it counteracts the cancer's influence on blood vessels in other parts of the body.

"Cancer spreads when cancer cells travel through the blood stream and settle and grow in other organs, like the lung or brain.

 "They are able to establish themselves in a distant body part because the primary tumor secretes substances that make blood vessels in other organs 'leaky,' or easier to penetrate.

"So when cancer cells travel in the blood stream they typically settle and grow where there are optimal conditions that have actually been created by the primary tumor.

"The primary tumor effectively 'talks' to the site where the metastasis is going to form so when the floating cancer cells arrive, they find a nice cozy environment in which to grow.

"While this behavior of cancer was already known, what we have discovered is that we can interfere with this process because of the way this new drug affects blood vessels.

"We've discovered it restores the leaky vessels which result in the cancer cells flowing past and not setting up shop.

"For a patient, this means that in future it will be possible to remove the primary tumor, then use the new drug to prevent cancer cells in the blood system from successfully attaching themselves to another organ and growing.

"But, if the cancer cells have already settled elsewhere and started growing then the drug can also be used to increase the number of immune cells brought into the new tumor to help it shrink."

"So we now have a drug that not only opens up the primary tumor for increased immunotherapy and greater treatment access, but it prevents metastatic spreading and if cancer has already spread, then the drug escalates the patient's immune response to new cancer.

"We now know we can interfere early and late in cancer's journey," Professor Ganss said.

Co-author of the publication, Dr. Bo He who undertook laboratory work on the drug said the research focused on metastatic cancer because most patients succumb to secondary cancers, not the primary.

"Using the drug that the team developed and published in 2017 in Nature Immunology we explored whether it could prevent metastases as well as improve patient immune response."

"We're quite excited that we have moved into a different phase of exploring how this drug could be used.

"So far we've successfully applied it to melanoma and lung cancer models in a metastatic setting," said Dr.

Watch the Video

https://scx2.b-cdn.net/gfx/video/2020/newdruglimit.mp4

https://www.perkins.org.au/news/new-drug-limits-cancer-spreading

Designed Molecules Trap Cancer Cells in Deadly Cages

Chemists have designed a carbohydrate-based molecule that can surround and strangle bone cancer cells by self-assembling into a tangled web of nanofibers (J. Am. Chem. Soc. 2014, DOI: 10.1021/ ja5111893). The molecule spares healthy cells because its assembly is triggered by an enzyme that’s overexpressed on cancer cells.

The inspiration for spinning a molecular cage around cells came from nature, says Rein V. Ulijn of the City University of New York’s Hunter College. Many of the body’s cells are enmeshed in an extracellular matrix—a complex web of biomolecules that provides structure for tissues, facilitates intercellular communication, and traps nutrients. Scientists are developing molecules that spontaneously assemble into simpler versions of this matrix to provide a growth medium for cells, in particular for tissue engineering.

The field has focused mainly on self-assembling peptides. In a recent study, Bing Xu of Brandeis University and colleagues designed a nonnurturing peptide that aggregates and engulfs cancer cells only when its phosphate group is removed (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201402216). The phosphate-free peptides have a hydrophilic end and a hydrophobic one, which allow them to assemble like lipids in a cell membrane. The negative charge on the phosphate groups creates electrostatic repulsion between the molecules and prevents this. This phosphate on-off switch is great for targeting cancer because some types of cancer cells overexpress alkaline phosphatase, an enzyme that cleaves phosphates.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/anie.201402216/abstract

Designed Molecules Trap Cancer Cells in Deadly Cages 

Bitter melon extract may have potential to fight head, neck cancer

Extract taken from an Asian vegetable may have therapeutic qualities to treat head and neck cancer, a Saint Louis University researcher has found. Preliminary findings of the research were published in the Public Library of Science One Journal by Ratna Ray, Ph.D. associate professor of pathology at Saint Louis University. Ray found that bitter melon extract, a vegetable commonly used in Indian and Chinese diets, reduces the head and neck cancer cell growth in the animal model.

"We wanted to see the effect of the bitter melon extract treatment on different types of cancer using different model systems," said Ray, who first tested the extract in breast and prostate cancer cells. "In this study, the bitter melon extract treatment suppressed the head and neck cancer cell growth in the mouse model, reducing the growth of the tumor."

In a controlled lab setting, Ray found that bitter melon extract regulated several pathways that helped reduce the head and neck cancer cell growth in the animal model. After a period of four weeks, Ray found that the growth and volume of the tumor had reduced.

Bitter melon is a tropical vegetable that is commonly used in Indian and Chinese cooking. Ray, who is originally from India, often uses bitter melon in her meals. People in Asia use this vegetable in stir fries, salads, and also drink its juice as part of a healthy diet.

Although more research is needed, Ray believes the bitter melon extract may enhance the current treatment option.

"It's difficult to measure the exact impact of bitter melon extract treatment on the cell growth, but a combination of things -- existing drug therapy along with bitter melon   may help the efficacy of the overall cancer treatment," Ray said.

Head and neck cancers, which account for 6 percent of all cancer cases, start in the mouth, nose, sinuses, voicebox and throat. They frequently are aggressive, and often spread from one part of the head or neck to another.

Before moving to phase I clinical trial with head and neck cancer patients, Ray said she and her team would need to validate their results with other preclinical models.

Ray's initial research found that treatment with this natural substance halted the breast and prostate cancer cell growth, eventually stopping them from spreading.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078006

Bitter melon extract may have potential to fight head, neck cancer

Research on soy-based treatment for colorectal cancer presented at AACR annual meeting

In continuation of my update on genistein

Genistein is one of several known isoflavones.Genistein was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name derived from the generic name. The compound nucleus was established in 1926, when it was found to be identical with prunetol. It was chemically synthesized in 1928.

Led by Randall Holcombe, MD, and Sofya Pintova, MD, both from Mount Sinai, the research team treated colon cancer cell lines with genistein and found that it inhibited cell growth and blocked Wnt signaling hyperactivity. The findings are counter to some other tumor types, such as breast, for which soy, because it has estrogen-like properties, increases the risk of developing tumors. Drs. Holcombe and Pintova are launching a clinical trial later this year for patients with metastatic colorectal cancer, which utilizes genistein in combination with chemotherapy based on this research.

"Genistein is a natural product with low toxicity and few side effects and our research shows that it may be beneficial in treating colorectal cancer," said Randall Holcombe, MD, Professor of Medicine in the Division if Hematology and Oncology at the Icahn School of Medicine at Mount Sinai. "This is an exciting area of research and we look forward to studying the benefits of this compound as an adjunctive treatment in colorectal cancer in humans."

Research on soy-based treatment for colorectal cancer presented at AACR annual meeting

Androgen receptors found to be a potential target in breast cancer

In continuation of my update on Enzalutamide

We know that, The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone  in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor...

Estrogen and progesterone receptors, and the gene HER2 - these are the big three markers and/or targets in breast cancer. Evidence presented at the AACR Annual Meeting 2013 adds a fourth: androgen receptors.

"This is a continuing line of work with all evidence pointing toward the addition of the androgen receptor as potential target and useful marker in all of the major subtypes of breast cancer," says Jennifer Richer, PhD, investigator at the University of Colorado Cancer Center and co-director of the CU Cancer Center Tissue Processing and Procurement Core.

 The finding of androgen receptors (AR) as a potential target in breast cancer is especially important in light of its prevalence in breast cancers that don't express other hormone receptor targets or have developed resistance to treatments that target estrogen dependence. Overall, approximately 77 percent of breast cancers are positive for AR, including 88 percent of cancers that are estrogen receptor positive, 59 percent of those that are HER2 positive, and 20-32 percent of triple negative breast cancers.....

Androgen receptors found to be a potential target in breast cancer

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic

In continuation of my update on Everolimus

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic

Treatment with everolimus led to tumor regression and  gnificantly improved survival compared  with placebo in mice with established lymphomas. However,  all  of  these  mice  eventually  relapsed as a result   of the growth of lymphoma  cells  resistant to the effec ts  of everolimus.

"These data confirmed our hypothesis that mTORC1 inhibition could suppress Myc-driven tumor initiation and growth," said McArthur. "The surprise was found in how mTORC1 inhibition led to tumor regression. We had expected that it would trigger cancer cells to die by a cellular process known as apoptosis, but we found that this was not the case."

Detailed analysis of the tumors indicated that everolimus caused tumor regression by inducing cellular senescence.

According to McArthur, normal cells protect themselves when cancer-driving genes are switched on is by entering a state called senescence. When cancers develop, they have found ways to overcome this safeguard. "Our data indicate that one way in which cancers bypass senescence, in particular senescence induced by Myc, is through a signaling pathway involving mTORC1," he said.

Resistance to everolimus treatment in mice with established lymphomas was associated with loss of the function of p53, a protein known to help suppress tumor formation and growth.

"The loss of effectiveness of everolimus therapy against lymphoma cells deficient in p53 function has important clinical implications," said McArthur. "Everolimus could be a useful new string to the bow for clinicians treating patients with Myc-driven cancers, in particular B cell lymphomas, but that it would be helpful only to those patients with functional p53."

Ref : http://cancerdiscovery.aacrjournals.org/content/early/2012/12/13/2159-8290.CD-12-0404.abstract?sid=79f94616-1798-4c19-92c2-26e76ad12905 

Astex Begins Phase 2 Cancer Trial | News | Drug Discovery and Development Magazine

Astex Begins Phase 2 Cancer Trial of  SGI-110 | News | Drug Discovery and Development Magazine

Cylene's Pol I inhibitor, CX-5461 activates p53 and selectively destroys cancer cells

Cylene Pharmaceuticals  announced that research collaborators at the Peter MacCallum Cancer Centre (Peter Mac) in Melbourne, Australia have established, for the first time, that RNA Polymerase I (Pol I) activity is essential for cancer cell survival and that its inhibition selectively activates p53 to kill tumors. Findings show that Cylene's Pol I inhibitor, CX-5461 (see structure), selectively destroys cancer by activating p53 in malignant but not in normal cells.

The researchers repeated these studies with in vivo models of blood cancers and demonstrated that the drug removed malignant cells from the bloodstream, while allowing normal healthy blood cells to grow, thus differentiating CX-5461 from genotoxic treatments. Targeting cancer's dependence upon Pol I to trigger cancer-specific activation of p53 signifies an entirely new approach to cancer therapy.

"The combination of cancer's reliance on Pol I, the impressive preclinical activity of CX-5461, the development of clear predictive and prognostic biomarkers and the novelty of the therapeutic strategy is compelling," continued Dr. Rice. "As such, a First-in-Human clinical trial with CX-5461 is planned in collaboration with our colleagues at Peter Mac later this year."

An unanticipated finding was that malignant cells are considerably more dependent upon maintenance of high levels of Pol I activity than previously believed, and even modest inhibition of Pol I triggers cancer cell death. These results suggest that selective activation of a surveillance pathway to activate p53, using Pol I inhibitors such as CX-5641, is likely to be therapeutically useful in the treatment of a wide range of tumors. In addition, as a cancer-specific inducer of p53, CX-5461 was shown to be 300 times more potent than currently studied non-genotoxic p53 activators with alternate mechanisms.

Cylene's Pol I inhibitor activates p53 and selectively destroys cancer cells

Skin cancer drug, vemurafenib may prolong survival in advanced cases: Study

In continuation of my update on vemurafenib...

According to an international study a new treatment for advanced skin cancer almost doubles survival times. Researchers say 132 patients in the U.S. and Australia who were given the drug vemurafenib gained several extra months of life. The treatment is one of two drugs for late-stage melanoma, approved on fast-track in the US last year, which offer hope for patients with advanced melanoma. Vemurafenib is suitable for about half of patients with advanced melanoma as it targets tumors that express a certain gene mutation. Before that, there had been no new drugs for the cancer for more than a decade...

More...

Coffee may protect against womb cancer: Study

 In continuation of my update on the benefits of coffee

A new study shows that regular intake of coffee may significantly lower risk for endometrial or womb cancer.

For the study the researchers looked at coffee consumption and endometrial cancer risk in more than 67,000 women aged between 34 and 59 enrolled in the long-running Nurses' Health Study. The researchers found that women who took more than four cups of coffee a day over a 26-year period were 25 percent less likely to get the cancer. Women who drank two to three cups a day were 7 percent less likely to get it. Drinking less than four cups a day was not associated with reduced risk. Furthermore drinking tea did not reduce the risk. Additionally drinking more than two cups of decaffeinated coffee a day was tied to a 22 percent reduced risk for endometrial cancer.

The benefit wasn't a complete surprise, since coffee has been shown to lower estrogen and insulin levels, and higher levels of these hormones have been associated with an increased risk of endometrial cancer. But the new findings do help to clarify how obesity, estrogen and coffee might interact in triggering tumors.

“It would be premature to make a recommendation that women drink coffee to lower their endometrial cancer risk,” study author Dr. Edward Giovannucci, professor of nutrition and epidemiology at Harvard School of Public Health...

Ref : http://cebp.aacrjournals.org/content/early/2011/10/03/1055-9965.EPI-11-0766.abstract?sid=d8d229ed-e4b4-4b7a-bc6a-f3f86cba4c0e

New dual drug combinations in development for various cancers

New dual drug combinations in development for various cancers: A rarely used—and as yet largely unproven—approach to drug development has emerged as a significant tool in the effort to create high-impact new cancer drugs.

Preclinical studies shows EmPAC more effective than Taxol

Cornerstone Pharmaceuticals, Inc. has announced the publication of data from preclinical studies on EmPAC™ (nanoparticle reformulation of paclitaxel). Company claims the data demonstrating improved safety and efficacy of EmPAC™ versus Taxol®, the generic formulation of paclitaxel and one of the most widely prescribed chemotherapies. EmPAC™ is a nanoemulsion formulation of Paclitaxel and is the lead product candidate of Cornerstone’s proprietary Emulsiphan™ cancer selective delivery nanotechnology platform. Taxol®, an injectable formulation of Paclitaxel, is currently used to treat a variety of cancers, including ovarian carcinomas, breast cancer, non-small cell lung cancer, and AIDS-related Kaposi’s sarcoma....

More : http://www.cornerstonepharma.com/wp-content/uploads/Empac-JNN-Release-FINAL-Sept_15_2011.pdf

Positive results from Plexxikon's vemurafenib Phase 2 and 3 trial against metastatic melanoma

We know that, PLX-4032(RG7204, Vemurafenib) is a highly selective inhibitor of BRAF kinase activity, with an IC50 of 44 nmol/L against V600E-mutant BRAF. BRAFV600E cancer-causing mutation occurs in most melanomas and about eight percent of all solid tumors....

More....

Coffee reduces prostate cancer risk

Coffee reduces prostate cancer risk

Clinical study: Celecoxib drug may treat breast cancer

In continuation of m update on Celecoxib

Clinical study: Celecoxib drug may treat breast cancer

AstraZeneca receives FDA approval for vandetanib to treat medullary thyroid cancer

In continuation of my update on Vandetanib,,,,,
AstraZeneca receives FDA approval for vandetanib to treat medullary thyroid cancer

Experimental drug effectively shuts off MCL1 gene and induces apoptosis

Structure -B (UNBS1450)

Experimental drug effectively shuts off MCL1 gene and induces apoptosis

Teaming broccoli with sprouts may make vegetable's anti-cancer effect twice as powerful

Teaming broccoli with sprouts may make vegetable's anti-cancer effect twice as powerful

Taxol reduces cell regeneration obstacles after spinal cord injury...

Scientists of the Max Planck Institute of Neurobiology in Martinsried and their colleagues from the Kennedy Krieger Institute and University of Miami in the United States, and the University of Utrecht in the Netherlands, have now shown that the cancer drug Taxol (see structure)  reduces both regeneration obstacles. Frank Bradke and his team at the Max Planck Institute of Neurobiology in Martinsried study the mechanisms inside CNS nerve cells responsible for stopping their growth. As per the claim by the researchers,  protein tubes (micro tubules) have a parallel arrangement in the tip of growing nerve cells, stabilizing cells and actively pushing the cell end forward. This arrangement is lost in injured CNS cells. So how can the order of the microtubule be kept or regained in these cells? And once the cells start growing, how can they overcome the barrier of the scar tissue? Together with their colleagues from the United States and the Netherlands, the Max Planck scientists have now found a common solution for both problems. Taxol, the trade name of a drug currently used for cancer treatment, has now been shown to promote regeneration of injured CNS-nerve cells.

Researchers claim that,  Taxol promotes regeneration of injured CNS-nerve cells in two ways: Taxol stabilizes the microtubules so that their order is maintained and the injured nerve cells regain their ability to grow. In addition, Taxol prevents the production of an inhibitory substance in the scar tissue. The scar tissue, though reduced by Taxol, will still develop at the site of injury and can thus carry out its protective function. Yet growing nerve cells are now better able to cross this barrier. 

"This is literally a small breakthrough", says Bradke.

Experiments in rats performed by this group verified the effects of Taxol. These researchers supplied the injury site after a partial spinal cord lesion with Taxol via a miniature pump. After just a few weeks, animals showed a significant improvement in their movements. So far researchers  tested the effects of Taxol immediately after a lesion.  Researchers next plan  is to investigate whether Taxol is as effective when applied onto an existing scar several months after the injury.  As the research is still in the state of basic research and a variety of obstacles remain  and eventually, pre-clinical trials will need to be done,  "however,  researchers believe that this is a very promising path........

Ref: Farida Hellal et. al., 

Discovery of a Biochemical Basis for Broccoli's Cancer-Fighting Ability

In continuation of my update on broccoli and its anticancer activity.....

Fung-Lung Chung and colleagues showed in previous experiments that substances called isothiocyanates (or ITCs)  found in broccoli, cauliflower, watercress, and other cruciferous vegetables appear to stop the growth of cancer. But nobody knew exactly how these substances work, a key to developing improved strategies for fighting cancer in humans. The tumor suppressor gene p53 appears to play a key role in keeping cells healthy and preventing them from starting the abnormal growth that is a hallmark of cancer. When mutated, p53 does not offer that protection, and those mutations occur in half of all human cancers. ITCs might work by targeting this gene, the report suggests.

Scientists studied the effects of certain naturally-occurring ITCs on a variety of cancer cells, including lung, breast and colon cancer, with and without the defective tumor suppressor gene. They found that ITCs are capable of removing the defective p53 protein but apparently leave the normal one alone. Drugs based on natural or custom-engineered ITCs could improve the effectiveness of current cancer treatments or lead to new strategies for treating and preventing cancer.

Ref : http://pubs.acs.org/doi/abs/10.1021/jm101199t