Experimental anti-cancer drugs PF-04691502 and PD-0325901 excel against colorectal cancer models

Genes make proteins and proteins tell your body's cells what to do: one talks to the next, which talks to the next, and to the next. Like a game of telephone, researchers call these  "signaling pathways". Abnormalities in these signaling pathways can cause the growth and survival of cancer cells. Commonly, mutations or rearrangements of genes in the MAPK  signaling pathway create cancer's fast growth, and alterations in the PI3K signaling pathway allow cancer cells to survive into virtual immortality.

Of course, researchers have extensively targeted these two signaling pathways, designing drugs that turn on or off genes in these pathways, thus interrupting the transmission of cancer-causing signals. Unfortunately, these pathways have proven difficult to drug and also it has been difficult to show the effectiveness of drugs that successfully interrupt the transmission of signals along these pathways.

A study by the University of Colorado Cancer Center published in the journal PLoS ONE and concurrent phase I clinical trial is examining a new strategy: targeting both these important cancer-causing pathways simultaneously.

"Well, these two pathways are mutated frequently in cancer. Why not hit both of them? It was as simplistic as that," says Todd Pitts, MS, research instructor in the Program for the Evaluation of Targeted Therapies, and the study's first author.

The study used colorectal cancer tumors grown on mice from samples of patient tumors, called "patient-derived xenograft" models. To these tumors, Pitts and colleagues added the experimental anti-cancer drugs PF-04691502 (left structure) and PD-0325901 (right structure), the first of which mutes a link in the PI3K signaling pathway and the second of which mutes a link in the MAPK signaling pathway. In this case, the combination was greater than the sum of the parts - alone, PF-04691502 and PD-0325901 modestly inhibit the growth and survival of colorectal cancer in these models; after 30-day exposure to the combination, colorectal cancer cells were killed much more effectively than by either drug alone, and even more effectively than if you added together the cells killed by each drug alone.

Experimental anti-cancer drugs PF-04691502 and PD-0325901 excel against colorectal cancer models

Experimental drug works best when patients' immune cells surrounding tumors express PD-L1

A promising experimental immunotherapy drug works best in patients whose immune defenses initially rally to attack the cancer but then are stymied by a molecular brake that shuts down the response, according to a new study led by researchers at Dana-Farber Cancer Institute and the Yale University School of Medicine.

The antibody drug, known as MPDL3280A, inhibits the brake protein, PD-L1, reviving the response by immune killer T cells, which target and destroy the cancer cells. In recent clinical trials, the PD-L1 checkpoint blocker caused impressive shrinkage of kidney, melanoma, and lung tumors. But, as with other immunotherapy drugs, many patients saw no benefit.

Researchers report in the November 27 edition of Nature that the antibody was most effective when the patients' immune cells surrounding tumors expressed PD-L1 - a sign that a pre-existing immune response had been shut down by PD-L1. There was less tumor shrinkage in patients who never developed an immune response to the cancer - and, as a result, had less PD-L1 in the cancer and surrounding tissues.

"I think this is a launching point to use these findings as a predictive biomarker," said F. Stephen Hodi, MD, of Dana-Farber, senior author of the report. Hodi directs the Center for Immuno-Oncology and the Melanoma Treatment Center at Dana-Farber. First author is Roy Herbst, MD, PhD, chief of Medical Oncology at the Yale Comprehensive Cancer Center.

The scientists studied tumor tissue samples from 175 patients treated in clinical trials with MPDL3280A for advanced non-small cell lung cancer, melanoma, kidney cancer, and other cancers. On average, 18 percent of the patients had complete or partial shrinkage of their tumors, with higher or lower rates in different cancer types. Overall, the treatment was well-tolerated, with few severe side-effects, the report said.

Ref : http://meetinglibrary.asco.org/content/83740?media=vm

Experimental drug works best when patients' immune cells surrounding tumors express PD-L1

Destroy Cancer Naturally in 40 Days

We know that, Tripterygium wilfordii, or léi gōng téng (Mandarin) (Chinese:雷公藤, Japanese: raikōtō), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine for treatment of fever, chills, edema and carbuncle.

Tripterygium wilfordii recently has been investigated as a treatment for a variety of disorders including rheumatoid arthritis,cancer, chronic hepatitis, chronic nephritis, ankylosing pondylitis, polycystic kidney disease as well as several skin disorders. It is also under investigation for its apparent antifertility effects, which it is speculated, may provide a basis for a Male oral contraceptive. Now University of Minnesota Masonic Cancer Center, researchers have reported that, ancient Chinese medicine is bringing renewed hope to cancer sufferers, all thanks to an herb called thunder god vine. For starters, this herb may make it possible to purge tumors from the body without resorting to chemotherapy or other intense interventions.

On top of that, early evidence shows thunder god vine could be particularly effective in hindering the growth of pancreatic, colorectal, and ovarian cancers, among others.

Destroy Cancer Naturally in 40 Days | Cancer Defeated

Chemotherapy drug combined with cancer-killing virus may treat recurrent ovarian cancer

In continuation of my update on doxorubicin

In six out of 10 cases, ovarian cancer is diagnosed when the disease is advanced and five-year survival is only 27 percent. A new study suggests that a cancer-killing virus combined with a chemotherapy drug might safely and effectively treat advanced or recurrent forms of the disease.

Researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), led the cell and animal study. Reporting in the journal Clinical Cancer Research, the researchers showed that the oncolytic virus called 34.5ENVE has significant antitumor activity against ovarian cancer on its own, and that its activity is even greater when combined with the chemotherapy drug doxorubicin in an animal model of disseminated peritoneal ovarian cancer.

"Our findings suggest that this could be a promising therapy, and we believe it should be further developed for the treatment of recurrent or refractory ovarian cancer in humans," says principal investigator Balveen Kaur, PhD, professor of neurological surgery and an OSUCCC - James researcher.

Among women treated for ovarian cancer whose tumors regress, 70 percent experience recurrence. The recurrent tumors are thought to develop from reserves of cancer stem-like cells that are chemotherapy-resistant and survive therapy. Consequently, recurrent tumors also tend to be resistant to primary chemotherapy regimens, and lethal.

The oncolytic herpes simplex virus 34.5ENVE is engineered to target cancer cells that overexpress the protein nestin and to inhibit the growth of blood vessels to tumors.

Chemotherapy drug combined with cancer-killing virus may treat recurrent ovarian cancer

Study reports anti-cancer activity in mice treated with experimental drug TAK-733

Study reports anti-cancer activity in mice treated with experimental drug TAK-733

TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc.

Ref: http://www.heemd.com/news/?md=1510006/
http://www.medchemexpress.com/TAK-733.html

Liver Cancer Drug Fails to Live Up to Early Promise...

In continuation of my update on everolimus

Although it looked promising in early studies, the drug everolimus didn't improve survival for people with advanced liver cancer in its latest trial, a new study found.

The findings from the phase 3 clinical trial are disappointing because earlier research suggested that everolimus (Afinitor) prevented tumor progression and improved survival for in advanced liver cancer. Normally, these patients can expect a median overall survival of less than one year.

The only drug currently shown to significantly improve survival of advanced liver cancer patients is sorafenib (Nexavar). But that drug's benefits are temporary and the cancer eventually progresses, according to background information in the new study.

The current study included 546 adults with advanced liver cancer whose disease progressed during or after treatment with sorafenib, or who could not take sorafenib. The patients were divided into two groups, with 362 given everolimus and 184 given a placebo.

Liver Cancer Drug Fails to Live Up to Early Promise 

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 

Two drugs in combination improve survival in patients with advanced pancreatic cancer

In continuation of my update on nab-paclitaxel (stands for nab-nanoparticle albumin-bound) and gemcitabine...

Investigators at the Vall d´Hebron University Hospital and the Vall d'Hebron Institute of Oncology (VHIO), have participated in an international phase III study, published in The New England Journal of Medicine. Results show that administering these two drugs in combination significantly improves one- and two-year survival in patients with advanced pancreatic cancer versus gemcitabine alone, the first-line treatment or most standard approach for this type of cancer to date.

The new drug is set to become a reference in advanced pancreatic cancer treatment. A multicentre phase III study, with centers participating from 11 countries in North America, Europe and Australia, shows that the drug combination nab-paclitaxel and gemcitabine is more effective in the treatment of patients with advanced pancreatic cancer than gemcitabine alone, which has been the standard treatment for these patients up until now.

The clinical trial, sponsored by Celgene Corporation, involved 861 patients, half of whom were administered the nab-paclitaxel/gemcitabine combination, while the other half received gemcitabine alone. Median overall survival was 8.5 months for nab-paclitaxel/gemcitabine versus 6.7 months for gemcitabine alone. One-year survival rates were 35% and 22%, respectively, and two-year survival rates were 9% and 4%, respectively. Similar side effects were found in the new drug and gemcitabine alike. The trial report therefore concluded that the nab-paclitaxel/gemcitabine combination significantly improves overall survival and response rate in patients with advanced pancreatic cancer.

Two drugs in combination improve survival in patients with advanced pancreatic cancer

Active ingredient of ipecac syrup inhibits growth of cancer cells

An old home remedy called ipecac syrup, once stocked in medicine cabinets in case of accidental poisoning, is showing promise as a new chemotherapy drug for bladder cancer.

Years ago, ipecac syrup was used to induce vomiting in poisoning cases. Now a Loyola University Medical Center study has found that the active ingredient of ipecac syrup effectively inhibits the growth of bladder cancer cells, especially when combined with a standard chemotherapy drug.

In the new study, Loyola researchers exposed cell lines of normal and cancerous bladder cells to emetine alone and to emetine plus cisplatin. (Cisplatin is the standard chemotherapy drug for advanced bladder cancer.)

• Emetine alone inhibits the proliferation of bladder cancer cell lines.
• Emetine acts synergistically with cisplatin to inhibit bladder cancer proliferation better than either drug does alone.
• Emetine has little effect on normal cells.

Bladder cancer is the fourth most common cancer in men and the 9th most common cancer in women. But even with aggressive surgery and chemotherapy, the five-year survival rate for patients with advanced Stage 4 bladder cancer is only 4 to 20 percent.

"There is an urgent need to develop new drug combinations," Dr. Gupta said. "Our study demonstrates that combining emetine with cisplatin is potentially beneficial, and merits further study in clinical trials."

Dr. Gupta is an assistant professor in the departments of Urology and Surgery and in the Oncology Research Institute of Loyola University Chicago Stritch School of Medicine. Dr. Foreman is an associate professor in the Department of Pathology and the Oncology Research Institute. Other authors are John Jesse III, a Stritch student, and Paul Kuo, MD, FACS, chair of Loyola's Department of Surgery and director of the Oncology Research Institute.

Ref : http://loyolamedicine.org/newswire/news/familiar-remedy-shows-promise-new-chemo-drug-bladder-cancer

Active ingredient of ipecac syrup inhibits growth of cancer cells

Smart anticancer 'nanofiber mesh'

A MANA research team has developed a new nanofiber mesh which is capable of simultaneously realizing thermotherapy (hyperthermia) and chemotherapy (treatment with anticancer drugs) of tumors. They succeeded in efficiently inducing natural death (apoptosis) of epithelial cancer cells.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/adfm.201300746/abstract;jsessionid=A14E178EC5E6FC5D367A7C71FF0D30BC.d02t01



Smart anticancer 'nanofiber mesh'

Aspirin May Fight Cancer by Slowing DNA Damage

Researchers hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. Researchers  evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5–8 time points over 6.4–19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1–8.6) off-NSAIDs and 0.6 (95% SI 0.3–1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two researchers detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs. More...

Aspirin May Fight Cancer by Slowing DNA Damage | ucsf.edu

Popular diabetes drug does not improve survival rates after cancer

In continuation of my update on metformin

Despite previous scientific studies that suggest diabetes drug metformin has anti-cancer properties, a new, first-of-its-kind study from Women's College Hospital has found the drug may not actually improve survival rates after breast cancer in certain patients.

The study, published in the journal Diabetes Care, failed to show an improved survival rate in older breast cancer patients with diabetes taking the drug metformin, a first-line treatment for diabetes. However, the authors caution further research is necessary to validate the study's findings.

"Metformin is a drug commonly used by diabetic patients to control the amount of glucose in their blood," said the study's lead author Dr. Iliana Lega, a research fellow at Women's College Research Institute. "Although existing scientific literature suggests that drug may prevent new cancers and death from breast cancer, our study found the drug did not significantly impact survival rates in our patients."

Scientific research has found metformin is associated with an up to 30 per cent reduction in new cancers and a reduction in tumour growth in non-diabetic breast cancer patients treated with the drug, Dr. Lega notes in the study.

To test the drug's anti-cancer properties, the authors examined 2,361 women, aged 66 or older who were treated with the drug and diagnosed with breast cancer between April 1, 1997 and March 31, 2008. The women were followed from their date of breast cancer diagnosis until their death or until March 30, 2010. The researchers found no significant statistical correlation between cumulative use of metformin and death from all causes or a significant reduction in deaths due to breast cancer.

"What makes our study so unique is that while the effects of metformin have been well documented, previous research has not examined the cumulative effects of the drug on patients, particularly breast cancer patients with diabetes," Dr. Lega said. "This is important given that diabetic patients may switch drugs over the course of their treatment."

The authors note a lack of data on body mass index, breast cancer stage and a short followup period for breast-cancer specific deaths, limit interpretation of their findings. Further research is necessary in a younger population of patients with breast cancer and diabetes.

"Understanding the effects of metformin on breast cancer patients is critical in helping address the gap in cancer outcomes in patients with and without diabetes," she added. "The findings will help physicians inform treatment plans for patients with diabetes."

Ref : http://care.diabetesjournals.org/content/early/2013/04/30/dc12-2535

Popular diabetes drug does not improve survival rates after cancer

Ganetespib Shows Potency Against Lung Cancer

In continuation of my update on Ganetespib

Ganetespib Shows Potency Against Lung Cancer

New chemo drug gentler on fertility, tougher on cancer

We know that, Arsenic trioxide is the inorganic compound with the formula As₂O₃. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tonnes are produced annually.Many applications are controversial given the high toxicity of arsenic compounds.

A Tiny Trojan Horse

The chemotherapy drug, arsenic trioxide, is packed into a very tiny Trojan horse called a nanobin. The nanobin consists of nano-size crystalline arsenic particles densely packed and encapsulated in a fat bubble. The fat bubble, a liposome, disguises the deadly cargo   half a million drug molecules.

"You have to wallop the tumor with a significant dose of arsenic but at the same time prevent exposure to normal tissue from the drug," said O'Halloran. The fat bubble is hundreds of times smaller than the average human cell. It is the perfect size to stealthily slip through holes in the leaky blood vessels that rapidly grow to feed tumors. The local environment of the tumor is often slightly acid; it is this acid that causes the nanobin to release its drug cargo and deliver a highly effective dose of arsenic where it is needed.

The scientists show this approach to packaging and delivering the active drug has the desired effect on the tumor cells but prevents damage to ovarian tissue, follicles or eggs.

While the drug is gentle on fertility, it is ferocious on cancer. When tested against lymphoma, it was more potent than the drug in its traditional free form.

"The drug was designed to maximize its effectiveness but reduce fertotoxicity," said O'Halloran, also the Morrison Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern. "Many cancer drugs cause sterilization, that's why the reproductive tract is really important to focus on in the new stages of drug design. Other body systems get better when people stop taking the drug, but fertility you can't recover."

Arsenic trioxide was approved a few years ago for treating some types of blood cancers such as leukemia in humans, but O'Halloran thinks the arsenic trioxide nanobins can be used against breast cancer and other solid tumors. In his previously published preclinical research, nanobins were effective in reducing tumor growth in triple-negative breast cancer, which often doesn't respond well to traditional chemotherapy and has a poor survival rate.

Quick Test For Fertility Toxicity

Woodruff was able to show early effects of the drug on fertility by using an in vitro follicle culture and a quick, simple new test she developed. She compared the fertotoxicity of the nanobin and free drug and found the nanobin was much less toxic to female fertility than the free drug in the experimental model.

"The system can be adapted very easily for any cancer drug under development to get an early peek under the tent,"said Woodruff, also the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg. "As this new drug goes forward in development, we can say this is a good drug for young female cancer patients who are concerned about fertility."

The information gained from the toxicity test will help inform the treatment decisions of oncologists and their young female cancer patients to improve their chances of creating a future family.

"They may prescribe less toxic drug regimens or refer them to specialists in fertility preservation," Woodruff said...

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058491

New chemo drug gentler on fertility, tougher on cancer

Soybeans can prevent cancer

Soybean meal is a bi-product following oil extraction from soybean seeds. It is rich in protein, which usually makes up around 40% of the nutritional components of the seeds and dependent on the line, and can also contain high oleic acid (a monounsaturated omega-9 fatty acid).

The study looked at the role soybeans could have in the prevention of cancer. Using a variety of soybean lines which were high in oleic acid and protein, the researchers looked to monitor bioactivity between the peptides derived from the meals of soybean and various types of human cancer cells.

The study showed that peptides derived from soybean meal significantly inhibited cell growth by 73% for colon cancer, 70% for liver cancer and 68% for lung cancer cells using human cell lines. This shows that the selected high oleic acid soybean lines could have a potential nutraceutical affect in helping to reduce the growth of several types of cancer cells.

Soybeans can prevent cancer

Researchers identifiy elusive anti-cancer property of vitamin E

Researchers identifiy elusive anti-cancer property of vitamin E

Bitter melon juice prevents pancreatic cancer in mouse models

"Three years ago researchers showed the effect of bitter melon extract on breast cancer cells only in a Petri dish. This study goes much, much farther. We used the juice  people especially in Asian countries are already consuming it in quantity. We show that it affects the glucose metabolism pathway to restrict energy and kill pancreatic cancer cells," says Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.

Agarwal's interest came from connecting the dots of existing research in a novel way. Diabetes tends to presage pancreatic cancer and bitter melon has been shown to effect type-II diabetes, and has been used for centuries against diabetes in the folk medicines of China and India. Following this line of thinking, Agarwal and colleagues wondered what would happen if they closed out the middle man of diabetes and directly explored the link between bitter melon and pancreatic cancer.

The result, Agarwal says, is, "Alteration in metabolic events in pancreatic cancer cells and an activation of the AMP-activated protein kinase, an enzyme that indicates low energy levels in the cells."

Perhaps not coincidentally, bitter melon also regulates insulin secretion by pancreatic beta cells. After studies in cell cultures, the group showed that mouse models of pancreatic cancer that were fed bitter melon juice were 60 percent less likely to develop the disease than controls.

"It's a very exciting finding," Agarwal says. "Many researchers are engineering new drugs to target cancer cells' ability to supply themselves with energy, and here we have a naturally-occurring compound that may do just that."

The Agarwal Lab is now applying for grants that will allow them to move the study of bitter melon into further chemoprevention trials in mouse models of pancreatic cancer.

Ref : dx.doi.org/10.1093/carcin/bgt081

 

Bitter melon juice prevents pancreatic cancer in mouse models

TIR-199 shows promise in fighting renal cancer

TIR-199 shows promise in fighting renal cancer

Ref : http://ucrtoday.ucr.edu/12020

Messenger RNA–Based Vaccines for Cancer | Articles | Drug Discovery and Development Magazine

Nucleic acids are being extensively investigated for use in gene therapy and in genetic vaccinations in which foreign nucleic acid is translated into proteins by the host cells. Vaccines based on DNA and messenger RNA (mRNA) are able to stimulate all effectors of the adaptive immune response: B lymphocytes, cytotoxic T cells, and T helper cells. This makes them a useful tool in the creation of prophylactic vaccines for infectious diseases and for cancer immunotherapy.

Messenger RNA–Based Vaccines for Cancer | Articles | Drug Discovery and Development Magazine

Vismodegib team wins Drug Discovery of the Year award

In continuation of my update on Vismodegib

Vismodegib team wins Drug Discovery of the Year award: The British Pharmacological Society proudly announces that its first annual Drug Discovery of the Year award has been won by the discovery team developing vismodegib for the treatment of basal cell carcinoma (a type of skin cancer).