Daffodils can fight cancer

A research describes the anti-cancer effects of a natural alkaloid extracted from Daffodils. Led by Denis Lafontaine, affiliated with the Faculty of Sciences at the ULB, the researchers have discovered that this compound triggers the activation of an anti-tumoral surveillance pathway.

 The researchers extracted a natural anti-cancer compound from Daffodils (Amaryllidaceae Narcissus). They established that this compound, an alkaloid named haemanthamine, binds to the ribosome. Ribosomes are nanomachines essential to the survival of humans cells because they synthesize all the required proteins. To sustain their unrestrained growth, cancer cells rely on increased protein synthesis: they are therefore particularly sensitive to treatments that inhibit the production and the function of ribosomes.

Haemanthamine blocks the production of protein by ribosomes, thus slowing growth of cancer cells. Haemanthamine also inhibits the production of these nanomachines in the nucleolus (the "ribosome factory"): this nucleolar stress triggers the activation of an anti-tumoral surveillance pathway leading to the stabilization of the protein p53 and to the elimination of cancer cells.

This study provides a molecular explanation to the anti-tumoral activity of Daffodils used for centuries in folk medicine. Haemanthamine belongs to a large family of therapeutic molecules of natural origin: numerous other alkaloids, used in human health, are extracted from plants, such as morphine (potent pain killer), quinine (anti-malarial agent), and ephedrine (anti-asthmatic).
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Treating aggressive colon tumor with immunotherapy

Immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind of therapy. Given this observation, researchers hypothesized that this kind of tumour was simply invisible to the immune system.

A team headed by ICREA researcher Eduard Batlle, at the Institute for Research in Biomedicine (IRB Barcelona), explains that the hormone TGF-beta is responsible for the "blindness" of the immune system to colon cancer cells. The few clinical immunotherapy trials done in patients with the most common subtype of colon cancer were not giving good results.

By inhibiting the activity of TGF-beta, the cells of the immune system infiltrate and recognise the tumour, fight the cancer, and even stop colon tumours from metastasizing to the liver and lung in a preclinical mouse model that mimics the human disease. In addition, and more importantly, the researchers demonstrated that the combination of a TGF-beta inhibitor with available immunotherapies boost the anti-tumour effect, allowing the immune system to efficiently eliminate already established metastases that would otherwise kill the individual in a question of weeks.

Scientist Daniele Tauriello, postdoctoral fellow and first author of the article, induced four of the most common mutations present in advanced human colon tumours in mice. After confirming the similarity of the mouse tumours with those in humans, they built a biobank of tumour organoids3-D mini-tumours and grafted them in a controlled manner in immunocompetent mice.

For studies of the immune system, the tumour has to be of mouse origin. Otherwise, the animal would reject it.This animal model which mimics the main features of metastatic colon cancer in humans, allowed the researchers to examine how cancer cells evade the immune system. Around 40 to 50 percent of colon cancer patients relapse in the form of metastasis, with the tumours reproducing mainly in the liver and lung.

Once advanced stage colon cancer is diagnosed, oncologists do not have access to efficient treatments to cure the patient. This study paves the way for the development of the first immunotherapy treatment for patients with metastatic colon cancer and for those patients with poor prognosis but who have not yet developed metastasis. Oncologists and pharmaceutical companies will soon start clinical assays that combine TGF-beta inhibitors, which are already in clinical use, with immunotherapies.

The researchers are convinced that many colon cancer patients will benefit from this therapeutic strategy. In the same issue of Nature, another study addresses the lack of response of bladder cancer patients to immunotherapy.  It appears that many types of tumour use the same strategy-increasing the expression of TGF-beta in the environment to evade the immune system. Patients with these tumours may also benefit from immunotherapies based on the inhibition of this hormone.
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Cancer-killing virus alerts immune system

A new UC San Francisco study has shown that a cancer-killing ("oncolytic") virus currently in clinical trials may function as a cancer vaccine-in addition to killing some cancer cells directly, the virus alerts the immune system to the presence of a tumor, triggering a powerful, widespread immune response that kills cancer cells far outside the virus-infected region.

Using novel approaches to examine exactly how oncolytic viruses attack tumors, issue of Cancer Research provided surprising insights about how a viral infection can cooperate with the immune system to attack cancer cells. The study highlights an opportunity to combine this form of therapy with cancer immunotherapy drugs such as checkpoint inhibitors, which unleash the immune system's full cancer-fighting power.

The idea that viruses could fight cancer goes back to the early 20th century, when doctors noted that cancer patients sometimes experienced dramatic remission after getting viral infections. Researchers have been developing oncolytic viruses since the 1980s, but following the U.S. Food and Drug Administration's 2015 approval of Amgen's Imlygic (T-Vec) as the first oncolytic viral therapy in the U.S., such viruses have become a closely watched area of therapeutic development.

Viruses appear capable of attacking tumors in a number of different ways by directly infecting them, by releasing tumor proteins that trigger a broad immune response against the cancer, and by damaging the blood supply tumors need to survive. To better understand the underlying mechanisms of these viral therapies, a collaboration was forged between UCSF vascular researcher Donald McDonald, MD, Ph.D., and researchers at San Francisco-based biotech SillaJen Biotherapeutics Inc. (formerly Jennerex Biotherapeutics, Inc.)

SillaJen is developing an oncolytic viral therapy called Pexa-Vec, currently in phase III and phase Ib/II clinical trials for use against primary liver and colorectal cancers, respectively. Pexa-Vec is an engineered virus based on the harmless vaccinia cowpox virus, also the basis for the original smallpox vaccine. Early observations suggesting that the virus might attack cancer in part by damaging blood vessels that feed tumor growth.

To study how the modified virus attacks tumors, researchers in the McDonald lab injected it intravenously into mice genetically modified to develop neuroendocrine pancreatic cancer. They found that the virus failed to infect healthy organs or make the animals ill, but succeeded in infecting blood vessels within tumors. These initial infections caused the vessels to leak and expose the tumor cells to the virus. In these experiments, the virus managed to infect and destroy only a small proportion of tumor cells directly, the researchers found, but within five days of the initial infection, the rest of the tumor began to be killed by a powerful immune reaction.

At first small spots of the tumor were infected, but then most of the tumor started to die. The researchers found that by killing some tumor cells directly, the viral infection exposed tumor proteins that could be detected by the immune system, triggering an immune attack on the rest of the tumor. The researchers demonstrated this by temporarily getting rid of the immune system's cancer-killing cells, called CD8+ or cytotoxic T cells, and showing that without these cells, the virus killed only the initial five percent of cancer cells.

When the researchers examined the tumors, they discovered that the second drug acted by making the immune system hyper-alert to tumor proteins released by the viral infection, rather than through effects on tumor blood vessels. This finding suggests that pairing Pexa-Vec's ability to awaken the immune system to previously ignored signs of cancer with the newest generation of checkpoint inhibitors, which act by unleashing the immune system's full force, might be an extremely potent combination therapy.
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Immunotherapy combination effective in patients with kidney cancer

Combining an anti-angiogenesis agent, which blocks blood vessel formation, with an immunotherapy agent, was found to have promising anti-tumor activity and no unexpected side effects in an early-phase clinical trial in patients with advanced kidney cancer who had not been previously treated, according to a researcher at the Georgetown Lombardi Comprehensive Cancer Center.

Axitinib inhibits angiogenesis, the process of blood vessels forming to feed a tumor. Inlyta was approved by the U.S. Food and Drug Administration in 2012 for the treatment of patients with advanced kidney cancer after one prior systemic therapy has failed, and has been shown to be selective in how it works, resulting in a strong effectiveness to toxicity ratio.

The immunotherapy agent, pembrolizumab, is an immune checkpoint inhibitor that blocks a self-defense mechanism used by cancer cells to evade attack and destruction by the body's immune cells. It is FDA-approved for the treatment of patients with several cancer types including melanoma, lung, bladder and head and neck cancers, but has only had limited study in patients with kidney cancer.

Earlier attempts to develop combinations of anti-angiogenesis agents and checkpoint-inhibitor-based immunotherapies to treat patients with advanced kidney cancer resulted in unacceptably high levels of toxicity and thus the combinations were not pursued further. In contrast, the axitinib-pembrolizumab combination was sufficiently tolerable to enable the agents to be given at their FDA-approved single-agent dose levels.

The combination doubled the efficacy of the drugs when used alone and the treatment was found to be tolerable," says Michael B. Atkins, MD, deputy director, Georgetown Lombardi Comprehensive Cancer Center and principal investigator for the study. "Specifically, over 90 percent of patients exhibited tumor shrinkage and the disease was kept under control for a median of over 20 months."

The investigators started their phase I clinical trial of this combination in 2014 and enrolled 52 advanced renal cell carcinoma (the most common form of kidney cancer ) patients who had not previously been treated for the disease. The enrollees received an intravenous infusion of pembrolizumab at the start of the trial and then every three weeks thereafter.

Patients also took axitinib twice daily until they could no longer tolerate the therapy or until no benefit was seen. The researchers looked at tumor size at trial enrollment, then 12 weeks later and every 6 weeks thereafter. In the 11-patient subgroup, three of the patients were not able to tolerate axitinib and received less than 75 percent of the planned dose due to toxicities, while eight patients experienced manageable side effects, thus establishing this dose level and the recommended dose level for further investigation in a group of 41 additional patients. Significantly, patients had fewer liver abnormalities and less fatigue than those treated with other similar combination therapies.

For the new combination therapy, tumor shrinkage or stabilization was better than what seen in patients taking just one of the two drugs alone. Seventy-three percent of patients experienced significant tumor shrinkage in response to the combination therapy and the median time in which there was no disease progression was 20.3 months. Overall survival results are still incomplete as 88 percent of the patients were still alive at a minimum 18 months after starting therapy.
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CAR-T- therapy safe and effective for leukemia

Results of the global, multicenter, pivotal phase 2 study that led to the first FDA approval of a gene therapy/cell therapy approach known as CAR T-cell therapy. The therapy, tisagenlecleucel, uses a patient's own white blood cells that have been genetically re-engineered to specifically target and kill cancer cells. It was approved to treat pediatric acute lymphoblastic leukemia (ALL), the most common childhood cancer. Senior authors on the study include Stephan A. Grupp, MD, PhD, of Children's Hospital of Philadelphia and Michael A. Pulsipher, MD, of Children's Hospital Los Angeles (CHLA).

 Researchers evaluate 75 patients between 3 to 21 years of age with relapsed or treatment refractory B-cell ALL. 61% of these patients had relapsed after allogeneic hematopoietic stem cell transplantation, an intensive therapy intended to be curative and whose failure leaves few remaining options. For comparison, the paper cites another FDA-approved therapy for the treatment of children with relapsed or refractory ALL; it produced a response rate of 20% with a median overall survival time of 13 weeks.

Patients who relapsed after transplant or did not respond to treatment - there wasn't much else we had to offer them and often, they went to hospice. Now, instead of sending them to hospice - we treat them with CAR-T-cells, make them better, then send them home. The updated analysis showed an overall remission rate of 81% within 3 months of treatment. All patients who responded to therapy showed no minimal residual disease by flow cytometry - the most sensitive means of analysis.

Overall survival was 90% at 6 months and 76% at 12 months. The median length of remission was not reached, with tisagenlecleucel remaining in the blood for up to 20 months. CAR-T therapy is truly a game changer for pediatric leukemia. Substantial side effects are associated with this therapy; grade 3 or 4 adverse events that may have been related to the therapy occurred in 73% of patients. The most significant side effects included cytokine release syndrome, often requiring admission to an intensive care unit, and neurological events in 40% of
patients.
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Broccoli can prevent colorectal cancer

Colorectal cancer is one of the most common cancers in the world, A team of researchers in the NUS Medicine lab of Associate Professor Matthew Chang have found a way to turn a humble bacteria and vegetables into a targeted system that seeks out and kills colorectal cancer cells. The study, which was led by Dr Chun-Loong Ho, will be published online today and in the current issue of Nature Biomedical Engineering.

At the heart of this cancer-targeting system is an engineered form of E. coli Nissle, a harmless type of bacteria found in the gut. Using genetic techniques, the team engineered the bacteria into a probiotic that attached to the surface of colorectal cancer cells and secreted an enzyme to convert a substance found in cruciferous vegetables (like broccoli) into a potent anticancer agent.

The idea was for the cancer cells in the vicinity to take up this anticancer agent and be killed. Normal cells cannot do this conversion, nor are they affected by the toxin, thus the system should be targeted only to colorectal cancer cells. True enough, the mixture of engineered probiotics with a broccoli extract or water containing the dietary substance killed more than 95% of colorectal cancer cells in a dish.

 Moreover, the mixture had no effect on cells from other types of cancer such as breast and stomach cancer. Strikingly, the probiotics-veggie combination reduced tumour numbers by 75% in mice with colorectal cancer. Also, the tumours that were detected in these mice were 3 times smaller than those in control mice which were not fed with the mixture.

These probiotics could be used in two ways: as prevention, to clean up the cancer cells remaining after surgical removal of tumours. Colorectal cancer patients may be able to take the probiotics as a dietary supplement along with their broccoli to prevent colorectal cancer or to reduce recurrence after cancer surgery.
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Novel compound for Melanoma cells

An international team of researchers has developed a novel compound that successfully inhibits growth of melanoma cells by targeting specific epigenetic modifying proteins in these cells. In the human body cells turn genes on and off by means of chemical modifications that change DNA and related proteins. These epigenetic changes are continuous and are at the core of how healthy cells transform into cancer cells.

These modifications contribute to a tumor's ability to grow indefinitely, as well as making tumor cells drug resistant and capable of surviving treatments intended to kill them. The new compound, Corin, specifically targets these epigenetic changes in cells and could therefore provide significant improvements in patients without unwanted side effects.

Currently there are few epigenetic drugs in clinical use, including histone deacetylase (HDAC 1) inhibitors, which are used to treat some lymphomas and histone demethylase inhibitors (LSD1) which are used to treat some leukemias. These reagents have not been more broadly useful in cancers due to their limited therapeutic window and untoward side effects.

Researchers at Boston University School of Medicine, Johns Hopkins University and Universiita di Pavia, Harvard Medical School and the University of Leicester collaborated to develop a unique compound, Corin that specifically act to inhibit both demethylase an deacetylase activity in cells. Corin is particularly attractive as an inhibitor of epigenetic modifications because it has dual-target specificity which allows for more selective targeting of epigenetic complexes in treated cells.

It is anticipated that this novel compound will have significant efficacy in human melanomas and other cancers either as a stand-alone therapy or in combination with other targeted or immune-based therapies.To evaluate the efficacy of this new compound, the researchers first tested it using a cell culture system to evaluate melanoma cell biology in vitro and found a variety of cancer-associated processes were affected, including cellular growth, differentiation and migration.

The compound then was tested in an experimental model for melanoma and found to significantly inhibit tumor cell growth without appreciable toxicities. The researchers believe there are other disease entities, apart from cancers, that may be significantly affected by targeted epigenetic therapies. Most notably, immune-mediated diseases are expected to be significantly influenced by such reagents as epigenetic changes have been widely noted to influence the immune system.
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Berry boosts cervical cancer therapy

According to the Centers for Disease Control and Prevention many women are diagnosed with cervical cancer each year. One of the most common treatments for cervical cancer is radiation. While radiation therapy destroys cancer cells, it also destroys nearby healthy cells. University of Missouri School of Medicine researchers studied in vitro human cancer cells to show that combining blueberry extract with radiation can increase the treatment's effectiveness.

Radiosensitizers are non-toxic chemicals that make cancer cells more responsive to radiation therapy. In a previous study, Fang and his research team showed that resveratrol, a compound in red grapes, could be used as a radiosensitizer for treating prostate cancer. Blueberries also contain resveratrol. In addition to resveratrol, blueberries also contain flavonoids.

The researchers used human cervical cancer cell lines to mimic clinical treatment. The cell lines were divided into four groups that included a control group, a group that received only radiation, a group that received only blueberry extract, and a group that received both radiation and the extract. Researchers used three different measures to confirm results of the study.

 Radiation decreased cancer cells by approximately 20 percent. Interestingly, the cell group that received only blueberry extract had a 25 percent decrease in cancer. However, the biggest decline in cancer cells occurred in the radiation and extract group.
The mechanism that makes blueberry extract a radiosensitizer also reduces the abnormal explosion of cell growth. Cancer cells avoid death by remodeling themselves. Along with reducing cell proliferation, the extract also 'tricks' cancer cells into dying. So it inhibits the birth and promotes the death of cancer cells.
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How cancer spreads

A University of Hawai'i Cancer Center researcher has identified how some cancer cells are made to move during metastasis. The research provides a better understanding of how cancer spreads and may create new opportunities for cancer drug development. Metastasis causes the deaths of 90 percent of cancer patients.

The spread of cancer by metastasis is driven by a set of mutant proteins called oncogenes which cause cancer cells to multiply uncontrollably and promotes their ability to move. How oncogene activity specifically directs the increased movement and metastasis is highly complex and remains largely unknown.

 RSK2 protein forms a signaling hub that includes proteins called LARG and RhoA. They show that turning on this signaling hub activates the movement of the cancer cells. These results significantly advance understanding of how cancer cells are made to move during metastasis and may provide more precise targets for drugs to stop cancer metastasis in patients where there are oncogenic mutations.
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DNA test for breast cancer

Scientists have developed a DNA test that may diagnose fatal breast cancer one year earlier than current methods. Changes in a part of DNA, which the researchers named EFC#93, suggests early warning signs of life-threatening breast cancer. These changes occur in patients' blood before their cancer becomes detectable in their breast tissue.

 A study revealed among women who have EFC#93 in their blood, 43 per cent were diagnosed with a life-threatening form of breast cancer three-to-six months later, while 25 per cent were diagnosed within six-to-12 months.

Markers such as EFC#93 provide a highly specific indicator that could diagnose fatal breast cancers up to one year in advance of current diagnosis.  This may enable individualised treatment, which could even begin in the absence of radiological evidence in the breast.

The researchers analysed EFC#93 in blood samples from breast cancer patients taken both after surgery but before chemotherapy and once chemotherapy was complete. They demonstrated DNA change in samples taken before chemotherapy as a marker for poor prognosis even if cancer cells are not yet circulating in the body.

 To assess whether EFC#93 can diagnose women with a poor prognosis earlier, the researchers then analysed samples of 925 healthy women, of which 229 went on to develop life-threatening breast cancer, while 231 got non-fatal forms of the disease within three years.
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Aspiring improves effectiveness of cancer treatment

Adding aspirin to some existing cancer drugs could increase their effectiveness against a group of tumours resistant to treatment, scientists are hoping clinical trials could soon be underway for people with lung, pancreatic and colorectal cancers that have not responded to other therapies.

Cancers driven by mutations in a group of genes, known as RAS, had a low response to treatments with currently no drug directly targeting them. The group of tumours includes some pancreatic, lung and colorectal cancers with very low survival rates, as well as a small percentage of melanomas.
Addition of aspirin to a cancer inhibitor drug, Sorafenib, strongly enhanced its effectiveness against mouse models of lung cancer and melanoma with RAS mutations.

In a multicentre phase three trial for non-small cell lung cancer, Sorafenib alone showed a marginal improvement for patients. Latest research suggests its combination with aspirin could benefit patients with RAS mutations who don't otherwise respond to other treatments.
The drug combination could potentially reduce the dose of Sorafenib required, improving quality of life for patients by reducing adverse impacts that can lead some patients to stop treatment.

Combining it with a relatively high dose of aspirin, two molecular processes are activated and together they work to kill RAS mutant cancer cells. This dual activation also might prevent the tumours acquiring resistance to the treatment, which can happen when the inhibitor drug is given alone.
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Natural immune suppressor responsible for early death in leukemia patients

Patients diagnosed with the most common form of leukemia who also have high levels of an enzyme known to suppress the immune system are most likely to die early. High levels of this enzyme, indoleamine 2,3 dioxygenase, or IDO, at diagnosis also identify those who might benefit most by taking an IDO inhibitor along with their standard therapy.

A review of patients with acute myeloid leukemia, or AML, found increased IDO expression in the bone marrow biopsy, performed to diagnose their disease, correlated with lower overall survival rates and early mortality. It also indicates that IDO expression should routinely be measured when the diagnostic bone marrow biopsy is performed, Everyone has the IDO gene, it's the cancer cells in this scenario that activate the disabler of the immune response that is also used by the fetus and solid tumors.

 Stem cells in the bone marrow are supposed to mature into a variety of cells that enable human blood and immune system function. Instead in AML, stem cells get stuck in an in-between, undifferentiated state called blasts.In leukemia, stem cells get limboed in the blast state so you don't get any maturation. That means there are low platelets so you get clotting problems, you have low neutrophils so you have infections, you have less red blood cells so you get anemic.

Bleeding is a major cause of death for patients and often, significant gum bleeding is the first indicator. The patients who died at six months had a high expression of IDO while the blasts produced relatively little IDO in the patients who lived five years or more. During pregnancy, cells in the placenta trigger an isolated suppression of the mother's immune system so it won't reject the genetically foreign fetus. They showed that IDO locally disables the mother's immune system by degrading tryptophan, an amino acid essential to survival of T cells , orchestrators of the immune system's response.

Later work would show that tumors - and leukemia - also use IDO to hide from the immune response. Conversely, some organ transplant patients who inexplicably express higher levels of IDO, have lower rejection rates of their new organ. Induction therapy is given to get the patient into remission, and is typically followed by more chemotherapy to ensure it stays dormant.
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Pomegranate extract alters breast cancer stem cell

Research team has found evidence suggesting that the same antioxidant that gives pomegranate fruit their vibrant red color can alter the characteristics of breast cancer stem cells, showing the superfood's potential for aiding in much more than diabetes or heart disease as previously thought.
Pomegranate extract, derived mainly from the skin of the fruit, is known for having high levels of powerful antioxidants called polyphenols.

Stem cells are unlike other types of cells in that they have a remarkable ability to self-divide and reproduce themselves, even giving rise to other types of cells. This self-dividing nature alone is not dangerous; in fact, normal tissue stem cells can replace dying cells and even repair damaged tissue.
The danger arises if stem cells become cancer stem cells, because their division and renewing ability carries over to cancer progression by aiding in tumor initiation, growth, and even re-initiating cancerous tumors long after a person has been declared cancer-free.

Compounding these issues are the fact that cancer stem cells are thought to be more resistant to therapy than other types of cancer cells. Cancer stem cells have become an important target in cancer therapy and prevention more so than other cancer cells, because of the idea that if the stem cells can be slowed or made "less stem-like," the cancer itself could be slowed too.

Researchers conducted experiments using cancer cells lines that are the prototypes of breast cancer stem cells. These cells, which display the exact properties of cancer stem cells, were treated with diluted pomegranate extract and incubated for periods ranging from one to six days.
During this time, the team measured several markers of breast cancer stem cells in both the pomegranate extract treated cells and untreated cells . They then compared the results between the groups and observed significant differences between the cancer stem cell prototypes that were treated with pomegranate extract.

Additionally, the cells that were treated with pomegranate extract were treated with relatively small amounts – thought to be manageable for a person to consume by simply purchasing the product at a grocery store and incorporating it into their diet. Low concentrations of the extract are able to modify the ability of cancer stem cells to reproduce themselves.

Pomegranate extract inhibits breast cancer cells ability to self-renew. Pomegranate extract converts cancer stem cells to cells that look like more traditional cancer cells and which may successfully be eliminated by cancer drugs.Pomegranate extract shows promising potential for having a positive effect in both the primary cancer prevention and inhibition of the disease progression.
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MicroRNA regulates movements of tumour cells

Cancer cells can reactivate a cellular process that is an essential part of embryonic development. This allows them to leave the primary tumor, penetrate the surrounding tissue and form metastases in peripheral organs.

During an embryo's development, epithelial cells can break away from the cell cluster, modify their cell type-specific properties, and migrate into other regions to form the desired structures. This process is known as an epithelial–mesenchymal transition EMT is reversible and can also proceed in the direction from mesenchymal cells to epithelial cells (MET).

It is repeated multiple times during embryonic development and ultimately paves the way for the formation of organs in the human body. Tumor cells can reactivate the program. Although this is a completely normal process during embryogenesis, it also plays an important role in the spread of tumor cells within the body and in the formation of metastases.

Tumor cells are able to reactivate the EMT/MET program. By doing so, they obtain characteristics of stem cells and develop strong resistance to classical and state-of-the-art targeted cancer therapies. An EMT also makes it easier for cancer cells to break away from the primary tumor, to penetrate into surrounding tissue and into blood vessels, to spread throughout the body and to form metastases in distant organs, which is ultimately responsible for the death of most cancer patients.

Regulation the cellular EMT program prevents the development of malignant tumors and the formation of metastases such as in the case of breast cancer, researchers focused specifically on microRNAs (miRNAs), a class of very short non-coding RNAs with a considerable effect on gene regulation.
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RNA molecules can kill cancer

Small RNA molecules developed as a tool to study gene function trigger a mechanism hidden in every cell that forces the cell to commit suicide.
The mechanism RNA suicide molecules can potentially be developed into a form of cancer therapy. Cancer cells treated with the RNA molecules never become resistant to them because they simultaneously eliminate multiple genes that cancer cells need for survival.

The inability of cancer cells to develop resistance to the molecules is a first, researchers discovered sequences in the human genome that when converted into small double-stranded RNA molecules trigger what they believe to be an ancient kill switch in cells to prevent cancer.

Testing a class of small RNAs, called small interfering (si)RNAs, researchers use to suppress gene activity. siRNAs are designed by taking short sequences of the gene to be targeted and converting them into double- stranded RNA. These siRNAs when introduced into cells suppress the expression of the gene they are derived from.

A large number of these small RNAs derived from certain genes did not, only suppress the gene they were designed against. They also killed all cancer cells. These special sequences are distributed throughout the human genome, embedded in multiple genes.
When converted to siRNAs, these sequences all act as highly trained super assassins.

They kill the cells by simultaneously eliminating the genes required for cell survival. By taking out these survivor genes, the assassin molecule activates multiple death cell pathways in parallel. The small RNA assassin molecules trigger a mechanism calls DISE, for Death Induced by Survival gene Elimination. Activating DISE in organisms with cancer might allow cancer cells to be eliminated.
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Origin of pelvic tumors in women

Some ovarian cancers start in the fallopian tubes. Ovarian cancer cells have more in common with cells covering the tips of fallopian tubes than with those on the surface of ovaries. If biomarkers can be found for these tubal cells, direct tests on tubal tissue might be able to detect ovarian cancer.

 The research team plans to conduct studies that will seek to apply the current molecular biology findings to clinical practice, removing a woman's fallopian tubes, but not her ovaries, may reduce the risk of ovarian cancer in those at high risk.

The current study confirm previous results that had suggested that many high-grade serious cancers in the pelvis are preceded by abnormal cells- lesions occurring in the fallopian tubes, called serous tubal intraepithelial carcinoma STIC.

Past studies in several cancer types had shown that cancer cells with different origins have different genetic profiles. Cancer cells may arise from clisertissue or may have spread to a location from another part of the body, but their genetic profile reflects the tissue of origin.

If STIC cells and ovarian cancer cells had different genetic profiles, they must have originated in different tissue types. Instead, in-depth molecular analyses of cells from different women with high-grade serous carcinoma failed to identify any genetic differences between cancer cells arising in the tubes and serous ovarian cancers occurring elsewhere in the pelvis.

Ovarian cancer is more aggressive than many other cancers because it is hard to diagnose in its earliest stage. Fewer than 50 percent of women diagnosed with the disease survive for longer than five years after their diagnoses.
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Blood cancer destroys bone marrow

Healthy bone marrow stromal
cells were made to transfer their power-generating mitochondria to other cancer cells, effectively feeding the acute myeloid leukaemia AML and supporting the leukaemia to grow.

AML act in a parasitic way by generating oxygen-deprived conditions in the bone marrow which stimulates the transfer of healthy mitochondria from the non-cancerous cells to the leukaemia cells.

An enzyme found in the AML cell membrane was shown to be responsible for creating the conditions necessary for mitochondrial transfer to occur. Researchers established that the enzyme called NOX-2 generated superoxide which drives this transfer.

The transfer takes place through AML-derived tunnelling nanotubes TNTs which link the cancer cells directly to the surrounding healthy cells.
Furthermore by inhibiting NOX-2, researchers showed a reduction in mitochondrial transfer took place which limited how much energy the AML cells could generate and resulted in slower cancer growth.
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Verzenio for treating breast cancer

Verzenio (abemaciclib) is approved to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a hormones (endocrine therapy).

Verzenio is approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It is also approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer had spread (metastasized).

Verzenio provides a new targeted treatment option for some patients with breast cancer who are not responding to treatment, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy.

Verzenio works by blocking certain molecules (known as cyclin-dependent kinases 4 and 6), involved in promoting the growth of cancer cells. Breast cancer is the most common form of cancer. The safety and efficacy of Verzenio in combination with fulvestrant were studied in a randomized trial in some patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and who had not received chemotherapy once the cancer had metastasized.

The study measured the length of time tumors did not grow after treatment (progression-free survival). The median progression-free survival for patients taking Verzenio with fulvestrant was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant.

The safety and efficacy of Verzenio as a stand-alone treatment were studied in a single-arm trial of 132 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and chemotherapy after the cancer metastasized.

 The study measured the percent of patients whose tumors completely or partially shrank after treatment. In the study, 19.7 percent of patients taking Verzenio experienced complete or partial shrinkage of their tumors for a median 8.6 months.

Common side effects of Verzenio include diarrhea, low levels of certain white blood cells (neutropenia and leukopenia), nausea, abdominal pain, infections, fatigue, low levels of red blood cells (anemia), decreased appetite, vomiting and headache.

Serious side effects of Verzenio include diarrhea, neutropenia, elevated liver blood tests and blood clots (deep venous thrombosis/pulmonary embolism). Women who are pregnant should not take Verzenio because it may cause harm to a developing fetus.
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Poliovirus therapy activates immune response against cancer

An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that prevent cancer cells to evade the immune system.

Glioblastoma is a lethal form of brain cancer. The research team elucidated how the poliovirus works not only to attack cancer cells directly, but also activates longer-lasting immune response that appears to inhibit regrowth of the tumor.

Using human melanoma and breast cancer cell lines, and then validating the findings in mouse models, the researchers found that the modified poliovirus therapy starts by attaching to malignant cells, which have an abundance of CD155 protein.

The CD155 protein is a poliovirus receptor. The modified virus then begins to attack the tumor cells, directly killing many, but not all. This releases tumor antigens. The second phase of assault is more complicated, by killing the cancer cells, the modified poliovirus triggers an alarm within the immune system, alerting the body's defenses to attack.

This appears to occur when the modified poliovirus infects dendritic cells and macrophages. Dendritic cells then present tumor to T cells to launch an immune response. Once the immune system is activated against the poliovirus-infected tumor, the cancer cells can no longer hide and they remain vulnerable to ongoing immune attack.

Poliovirus killed tumor cells and infected the antigen-presenting cells, which allows them to function in such a way that they can raise a T-cell response that can recognize and infiltrate a tumor. Poliovirus stimulates an innate inflammatory response.
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Growing tumors evade anti-tumor immunity

The immunological pressure occurring during tumor progression might be harmful for the tumor to survive but the cancer cells evade the condition by restraining the anti-tumor immune response.

Cancerous tumors often grow so fast that they use up their available blood supply, creating a low-oxygen environment called hypoxia. Cells normally start to self-destruct under hypoxia, but in some tumors, the microenvironment surrounding hypoxic tumor tissue has been discovered to protect the tumor with the help of MicroRNA.

MicroRNAs are small, noncoding RNA molecules that regulate genes by silencing RNA, they have increasingly been implicated in tumor survival and progression. Researchers examined different types of tumor for altered levels of microRNAs. They identified two microRNAs ;miR25 and miR93 whose levels increased in hypoxic tumors.

The team then measured levels of those two microRNAs in the tumors of cancer patients and found that tumors with high levels of miR25 and miR93 led to a worse prognosis in patients compared to tumors with lower levels. The reverse was true for another molecule called cGAS: the lower the level of cGAS in a tumor, the worse the prognosis for the patient.
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