New research suggests cancer may not be eradicated

The National Cancer Institute has poured massive funds into cancer research, and big Pharmas have developed targets-based blockbusters. Yet a cure remains elusive.


To effectively treat patients with cancer, scientist and doctors have to interfere with fundamental pathways, which make up interaction network. However in some cases, Inhibiting one pathway can’t act as anticancer effectiveness, because of the crosstalk between multiple pathways. That’s why cancer “will probably never be completely eradicated.”

A novel research, published in Nature Communications, suggests that cancer can’t be eradicated. The researchers discovered that hydra, emerged hundreds of millions of years ago, forms tumors similar to those found in humans. It reflects that our cells’ ability to develop cancer is “an intrinsic property” that has evolved.

In the previous study, scientists showed that pulsating polyps carry genes that can cause cancer in humans. To unravel the tumor-causing mechanisms, They discovered tumor-ridden polyps, and saw that stem cells -programmed to turn into female sex cells- divided uncontrollably resembling ovarian cancer in women. Subsequently, they sequenced the tumorous hydra’s DNA and discovered a gene that halts apoptosis, and the activity of which runs amok in tumor tissue.

As known, tumors can grow in hydra, but are hydra tumors invasive the way they are in humans? To find out, the researchers transplanted tumors into healthy polyps. The cells from tumors transplanted in the midsections of healthy polyps migrated all the way to both ends of their bodies.

All this means that cancer genes and the mechanisms that allow tumor cells to evade death and invade healthy tissue, have deep evolutionary roots. Any crucial cell in body can at any point make a mistake, and there’s no way to prevent it.


Naturally occurring tumours in the basal metazoan Hydra. Nature Communications, 2014. 24;5:4222

Nano-robots seek and destroy tumours

Tiny robots, patrolling human body, search for malignant tumors and destroy them from within. It shows the prospect of being a realistic scenario, rather than a science fiction. What happens in biomedical industry is that a multi-purpose anti-tumour nanoparticle called “nanoporphyrin” is being developed to help diagnose and treat cancers.


The research, published in Nature Communications, shows that the advent of medically important nano-robot may not be far off. It is believed to efficiently and safely diagnose and treat the patients with cancer.

“Soft” organic nanoparticle acts as drug-delivery carriers, some of which have been proved or are in clinical trials for tumour treatment. Its small size offers an intrinsic advantage as it can be engulfed by and accumulated in tumour cells, where it can act on two levels: to aid diagnosis in enhancing the contrast on the molecule level; To be loaded with anti-tumour drugs on the micelle level.

Armed with anti-tumour drugs

The armed nano-robot particles can target and deliver the drug into tumour tissue, when a tumour-recognition module is installed in a delivery nano-robot (organic particle). They kill only those cells, while being harmless to surrounding healthy cells and tissues.

If a tumour-recognition module is installed in a probe nano-robot (inorganic particle), the armed nano-robot particles can get into tumour tissue and activate a measurable signal to help doctors better diagnose tumours.

It has been a huge challenge to integrate these functions on the one nanoparticle. It’s difficult to combine the imaging functions and light-absorbing ability for phototherapy in organic nanoparticles as drug carriers. This has, until now, hampered development of smart and versatile “all-in one” organic nanoparticles for tumour diagnosis and treatment.


A smart and versatile theranostic nanomedicine platform based on nanoporphyrin. Nature Communications; 2014.

Choosing the most effective cure for chronic myeloid leukemia

Recent research, published in the journal Cancer Cell, reports that scientists have identified and characterized mutated versions of the genes that encoding BCR-ABL, the unregulated enzyme driving the blood cancer chronic myeloid leukemia (CML).


Tyrosine kinase inhibitors (TKIs), targeted on BCR-ABL, are already in use, and are effective at controlling the disease. They do not cure CML but control it in a way that allows patients to get back to normal life and a normal expected lifespan. Before the arrival of TKIs, the 5-year survival rate for CML was 30% at best; now that figure is above 95%.

As indicated in trials, most cases of CML resistance are derived from a single mutation in BCR-ABL, and drugs to control resistance to TKI treatment caused by various single mutations have already been discovered. But BCR-ABL compound mutants that contain 2 mutations in the same molecule make some or all of the available TKIs ineffective.

The research team focused on BCR-ABL compound mutants observed in patients and tested them against all approved TKIs, creating a dataset that can potentially help clinicians decide which drug will be most effective for each mutation combination. They found that none of the TKIs are effective for some compound mutations, indicating the need for further research to accommodate the increasing population of CML patients.

Scientists sequenced about 100 clinical samples, which rendered a large body of data to shed light on the number of compound mutations and how they develop. One key finding was that compound mutations containing an already known mutation called T315I tend to confer complete resistance to all available TKIs.


 BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia. Cancer Cell, 2014

Targeting EphA3 to treat solid tumors

Scientists present a finding – published in the journal Cancer Research- that an antibody against the protein EphA3 has antitumor effects, providing a new approach to treat solid tumors.

As EphA3 is present in normal organs only during embryonic development but is expressed in solid tumors, this antibody-based approach may be a suitable candidate treatment for solid tumors.



Tumor cells, without EphA3 in itself, can thrive by recruiting and taking advantage of supporting EphA3-containing cells in the tumor microenvironment.

As we know, the tumor cells send out signals to the surrounding area, seeking a blood supply and a foundation upon which to spread. And EphA3-expressing stromal stem cells, once receiving signals, can form cells that support and create blood vessels in tumors.

In the experiment where human prostate cancer cells were introduced into a mouse model, researchers found EphA3 in stromal cells and blood vessels surrounding the tumor.

 Also, they observed the treatment with an antibody against EphA3 (chIIIA4) significantly slowed tumor growth. The antibody damaged tumor blood vessels and disrupted the stromal micro-environment, and cancer cells died because their ‘life-support’ was compromised.

 The microenvironment is so important for tumor cell survival that monoclonal antibodies against EphA3 can act as one way to kill a variety of solid tumors by disrupting their microenvironment.

Currently, KaloBios Pharmaceuticals is testing the anti-EphA3 antibody KB004 in a multi-centre Phase I/II clinical trial in Melbourne and the US in patients with EphA3-expressing blood malignancies: AML, MDS and myelofibrosis.


Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment. Cancer Research, 2014; 74 (16): 4470

Natural killing cells linked with MCL-1 could prevent cancer spread

A novel research highlights that highly specialized immune cells, called natural killer cells, play critical important role in killing melanoma cells that have spread to the lungs. As reported,  these natural killer cells could be harnessed to hunt down and kill cancers that have spread in the body.


The discoveries come after investigators showed that a protein called MCL-1 was crucial for survival of natural killer cells, in research appearing in the August 24th journal of Nature communication. And the discoveries will help to determine how natural killer cells can be manipulated to fight cancers.

MCL-1 levels inside the cell increase in response to a blood cell signalling protein called interleukin 15 (IL-15). As known previously, IL-15 increasing production was associated with survival of natural killer cells. This current research shows that IL-15 does this by initiating a cascade of signals that tell the natural killer cell to produce MCL-1 to keep it alive.

Investigators speculate that MCL-1 could be a target for boosting or depleting natural killer cell populations to treat disease, based on the discovery that the molecule is absolutely essential for keeping natural killer cells alive.

Natural killer cells are immune predators, patrolling the body in search of foreign invaders, and sensing changes in our own cells that are associated with cancer. Without these cells, the body was unable to destroy melanoma metastases that had spread throughout the body, and the cancers overwhelmed the lungs.

However these predatory natural killer cells are a double-edged sword. Investigators find natural killer cells were critical to the body’s rejection of donor bone marrow transplants and in the runaway immune response during toxic shock syndrome.

Reference:Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. Nature Communications, 2014; 5

Bacteria therapy could be effective in killing cancer

A study, published in Science Transnational Medicine, reports that tissue-damaging bacteria have been successfully employed in individualized treatment of tumors in rats, dogs. While final results of the ongoing trials in humans are unknown, scientists say that more studies are needed to find out the response to bacteria in patients.


The microbe Clostridium novyi, found in oxygen-poor environments, was modified to remove some of its toxicity and then targeted on oxygen-starved tumour cells. In the experiment of its direct injection into 16 dogs’ soft-tissue tumours, 3 showed reduction in the size of tumour by 30%, and 6 showed anti-cancer response.

Additionally, a clinical trial was conducted on one patient with a tumor in the abdomen. The result displayed that tumor reduced significantly. The study has focused on soft tissue tumor as these are usually locally advanced and spread into normal tissue. The bacteria cannot survive in normal tissues and will home in on the oxygen-starved tumor cells.

Bacteria therapy was first tried in rats where it was seen that bacteria avoided healthy cells and attacked the tumor alone. The treatment also improved their survival, with treated rats surviving an average of 33 days after bacterial injection as opposed to 18 days in rats that were not treated.

Bacteria have been used in tumour treatment for decades. Earliest accounts are from an immunotherapy called Coley toxins following cancer remission in patients who contracted serious bacterial infections.

Reference :

Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Sci Transl Med,2014. 6(249): 249ra111

PALB mutation raises the risk of breast cancer dramatically

In a new study appearing in the Aug. 7 issue of the New England Journal of Medicine, mutated versions of a gene called PALB2 can dramatically increase a woman’s risk of breast cancer. Women carrying the PALB2 mutation have a one-in-three probability of developing breast cancer by the age of 70.

The investigators found that the risk is even higher -reaching up to about six in 10- for women with a family history of breast cancer. Those odds place PALB2 just behind the BRCA1 and BRCA2 genes as a top genetic risk factor for breast cancer.



PALB tied to major breast cancer risk

For breast cancer, both BRCA genes have became the predominant biomarkers to evaluate a woman’s risk. According to the U.S. National Cancer Institute, Women who carry a mutated form of either of the BRCA genes have a 45% to 65% risk of breast cancer by age 70.

This new study provides the first solid evidence regarding the breast cancer risk associated with PALB2. Knowing this knowledge, women with a PALB2 mutation can talk with their doctor about whether they should undergo a surgery to reduce their breast cancer risk.

BRCA1, BRCA2 and PALB2 all play a significant role in the repair of damaged DNA. From the perspective of mechanism, PALB2 interacts with BRCA2, and acts as a kind of a bridge between BRCA1 and BRCA2. Mutation of any of the genes impairs the body’s ability to fix broken DNA, which can lead to cancer.


Breast-Cancer Risk in Families with Mutations in PALB2. N Engl J Med 2014; 371:497-506

New cancer classification system help better treat patients

A new study, published in the journal Cell, found that classifying cancer tumors by their molecular structure instead of the tissue or organ may lead to more accurate diagnoses and potentially better treatments and outcomes for patients.


Through analyzing over 3,500 samples from 12 cancer types -such as breast, kidney and bladder,    researchers found at least 10% of tumors (possibly as high as 30 to 50 % ) would be identified differently if oncologists determined their diagnoses by a tumor’s molecular makeup.

Additionally , tumor samples on a molecular level appeared to look more like unrelated cancers. For an instance, a significant number of squamous head-and-neck cancers looked more like some squamous-cell cancers found in the lung.

They also found that in many of the cancer types, such as an aggressive form of brain tumor known as glioblastoma and a type of leukemia, the tumor samples matched up well with the tissue classifications, suggesting that a tumor’s location is still important for certain types of cancers.

Usage for New cancer classification system

Many cancers, which are yet sequenced, are added into the genomic “map”, including breast, kidney, bladder, brain, colon, endometrial and lung. It enable doctors to figure out whether an existing therapy for one cancer will work for a subtype of a seemingly different cancer.

The discovery that some tumors shared molecular similarities with tumors from other parts of the body was particularly striking in bladder cancer. It may help explain why some bladder cancer patients respond much differently to treatment than others.


Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin. Cell.2014.06.049



CRISPR -an alternative way to model cancer

As known previously, the common practice in modeling cancer is to reveal mutations by sequencing its genomes and then to discover the role of these mutations in the course of breeding certainly mutated mice. And now, researchers can rapidly model cancer by using CRISPR, a gene-editing system introducing cancer-causing mutations into the livers of adult mice.


In a study appearing in the Aug. 6 issue of Nature, the researchers generated liver tumors in adult mice by disrupting the tumor suppressor genes p53 and pten. They are currently working on ways to deliver the necessary CRISPR components to other organs, allowing them to investigate mutations found in other types of cancer.

The sequencing of human tumors, based on high throughput technique, has revealed hundreds of oncogenes and tumor suppressor genes in different combinations. The flexibility of CRISPR, as delivery gets better in the future, will present a way to pretty rapidly test those combinations.

CRISPR relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this bacterial system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.

Using Cas enzymes targeted to cut small fragments of p53 and pten, the researchers were able to disrupt those 2 genes in about 3 percent of liver cells, enough to produce liver tumors within 3 months.

Usage for CRISPR

The researchers also used CRISPR to create a mouse model with an oncogene called beta catenin, which makes cells more likely to become cancerous if additional mutations occur later on. To create this model, the researchers had to cut out the normal version of the gene and replace it with an overactive form, which was successful in about 0.5 % of hepatocytes.

In this study, the researchers delivered the genes necessary for CRISPR through injections into veins in the tails of the mice. While this is an effective way to get genetic material to the liver, it would not work for other organs of interest. However, nanoparticles and other delivery methods now being developed for DNA and RNA could prove more effective in targeting other organs, Sharp says.


CRISPR-mediated direct mutation of cancer genes.Nature,2014. doi:10.1038/nature13589

Predict oral cancer recurrence from blood and saliva

It’s good news for a substantial number of patients that scientists have developed blood and saliva tests that help accurately predict returns of HPV-linked oral cancers. As known, the tests screen for DNA fragments of the human papillomavirus (HPV) shed from cancer cells lingering in the mouth or other parts of the body.

Patients with such cancers are generally examined every one to three months in the first year after diagnosis. Recurrences are often found when patients experience ulcers, pain or lumps in the neck. However imaging tests are unreliable in detecting cancer recurrence earlier, and the location of oropharyngeal cancers make it difficult for physicians to spot budding lesions.



A investigator says, “There is a window of opportunity in the year after initial therapy to take an aggressive approach to spotting recurrences and intensively addressing them while they are still highly treatable. Until now, there has been no reliable biological way to identify which patients are at higher risk for recurrence, so these tests should greatly help do so.”

High predictive value for recurrence

For the study, investigators analyzed blood and saliva samples from 93 oropharyngeal cancer patients including 81 patients with HPV-positive tumors, and found that HPV DNA detected in both blood and saliva samples after treatment was predictive for recurrence nearly 70% of the time in a subset of the patients.

Scientists are seeking other genomic biomarkers that would increase the specificity of HPV DNA testing in blood and saliva. Meanwhile, What is alarming is that the research is too small to link test results to the severity of recurrence.


Saliva and Plasma Quantitative Polymerase Chain Reaction–Based Detection and Surveillance of Human Papillomavirus–Related Head and Neck Cancer. JAMA Otolaryngology–Head & Neck Surgery, 2014