A study from a research group in Memorial Sloan Kettering Cancer Center has reported, for the first time, the success in the long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. This finding will provide an exciting new tool to test cancer drugs and individualized cancer approach. This result was published in Cell.
Prostate cancer is the most common malignancy and the second most common cause of cancer death in Western men. The American Cancer Society estimates that there will be 233,000 new cases of prostate cancer diagnosed in United States in 2014. However, the lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response.
In this research, scientists have successfully cultivated seven human-derived prostate cancer organoid lines derived from diverse disease sites including circulating tumor cells. These organoid lines are first fully characterized ones that recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss.
With these oragniod lines, the researchers have got the new source that could be used to control and capture the molecular diversity of prostate cancer. It will be a valuable tool to test the drug sensitivity. This methodology should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.
Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., … & Chen, Y. (2014). Organoid Cultures Derived from Patients with Advanced Prostate Cancer. Cell.
Researchers from University of North Carolina have recently identified a critical splicing factor RBM4 whose expression decreases dramatically in many human cancers, including lung cancer and breast cancer, etc. This result may provide ideas that would enable therapeutic targeting of deregulated splicing and open new avenues for cancer therapy. This study was published on Cancer Cell.
Alternative Spicing(AS) plays a vital role in the intricate regulation of protein function and aberrant splicing is closely associated with human cancers. However, the mechanistic details underlying these connections are largely unknown. Investigating splicing factors that play vital roles in cancer progression is a promising way to find the therapeutic anti-cancer target.
In this research, scientists report a splicing factor RBM4 suppresses proliferation and migration of various cancer cells by specifically controlling cancer-related splicing. RBM4 could regulate Bcl-x splicing to induce apoptosis, and coexpression of Bcl-xL partially reverses the RBM4-mediated tumor suppression. Further, RBM4 antagonizes an oncogenic splicing factor, SRSF1, to inhibit mTOR activation. Among many cancer patients, RBM4 expression stays in a very low level and its level correlates positively with improved survival.
This study represents a detailed mechanism of cancer-related splicing dysregulation and establishes RBM4 as a tumor suppressor with therapeutic potential.
Wang, Y., Chen, D., Qian, H., Tsai, Y. S., Shao, S., Liu, Q., … & Wang, Z. (2014). The Splicing Factor RBM4 Controls Apoptosis, Proliferation, and Migration to Suppress Tumor Progression. Cancer cell, 26(3), 374-389.
A recent study appearing in Nature Genetics reports that 23 new risk sites are found in the process of analyzing over 10 million genetic markers in 80,000 men with prostate cancer. In addition to 76 identified previously, 100 Prostate Cancer Risk Loci are higher than other cancer ones identified.
In the largest-ever analysis of the cancer’s genetic biomarkers, scientists are looking for the combination effect of how 100 loci work together and how much they can explain the heritability of prostate cancer. What they have learnt is that one should rely on the total of the 100 Loci, rather than one gene , to predict risk.
Investigators find that the top 1% of men with these variants have a 5.7-fold relative risk compared with the population average, and only 10% of prostate cancers are the aggressive form.
The indications from the research are that these genetic variants explain 33% of the familial risk of the disease, and some risk variants are more common in different ethnic population. For instance, the aggressive form is prevalent in Africa and they find some risk genes specific to African populations.
Next research steps include the sample collections from 100,000 people with prostate cancer and the larger- scale analysis using huge datasets. The goal of future research is to predict the aggressive form before it goes on to spread because even after the prostate is removed a few cells can go on to kill the person.
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature Genetics, 2014
As is commonly known in the biomedical community, predicting how prostate cancer will progress has been much like flipping a coin. But a new discovery could change that by enhancing the prediction accuracy.
Investigators analyzed the genetic data in the cells of nearly 300 prostate cancer samples and found certain fragment mismatches called “fusions” in the patients who had recurrent cancer despite removal of the prostate.
Normally, Genomic DNA is lined up in the cells in a very organized fashion, but in cancer cells, it appears the DNA gets mixed up where a piece of one gene is attached to the piece of another gene. The fusions result in the genes unable to make proteins to suppress tumor growth, and the cancer grows more vigorously.
There is about 90% chance to be a recurrence of prostate cancer if one have fusions. So clinicians can give correct judges based on this high number, thereby providing effective therapeutic regimens, such as removal of the prostate and hormone therapy.
A researcher said, “We’re in the process of validating this in a larger set of patients, though I expect one day there will be a test you can order, And tests like this may be helpful in deciding is it safe for us to do active surveillance or not in your case.”
Supervised Multi-View Canonical Correlation Analysis (sMVCCA): Integrating histologic and proteomic features for predicting recurrent prostate cancer. IEEE Trans Med Imaging. 2014 Sep 5.
Researchers from University of California, San Diego have identified an enzyme that controls the spread of breast cancer. This finding was reported in PNAS and offer new insights of understanding the metastasis of breast cancer.
Breast cancer is the leading invasive cancer among women worldwide. Its metastatic recurrence can happen many years after the removal of the primary tumor and cause the mortality. The current treatments ,including surgical removal and localized radiotherapy, are effective against primary Breast cancer, but could do little to prevent metastatic recurrence. Even Chemotherapy is not helpful to prevent metastatic recurrence.
In this study, researchers have demonstrated an ubiquitin conjugating enzyme Ubc13, which could catalyze K63-linked protein polyubiquitination, is largely dispensable for primary mammary tumor growth but is required for metastatic spread and lung colonization by Breast cancer cells. Ubc13 is required for TGFβ-induced non-SMAD signaling via TAK1 and p38, a pathway that is first activated in the primary tumor. The study has identified an Ucb13- and p38-dependent metastatic gene signature , explaining how p38 may control metastasis and providing a measure for monitoring the effectiveness of pharmacologic p38 inhibition, which inhibits the growth of established metastatic lesions. It suggests that p38 inhibition should be considered as a potential treatment for metastatic breast cancer.
Wu, X., Zhang, W., Font-Burgada, J., Palmer, T., Hamil, A. S., Biswas, S. K., … & Karin, M. (2014). Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1-p38 MAP kinase cascade.Proceedings of the National Academy of Sciences, 201414358.
A study, published in the journal Integrative Cancer Therapies, provides compelling evidence that cancers hidden beneath the skin can be detected simply by examining the odors of a person’s breath. It means that after a few weeks of basic “puppy training”, dogs can accurately distinguish between breath samples of lung- and breast-cancer patients and healthy subjects.
Some types of Cancer patients take a breath out with patterns of biochemical markers, since cancer cells emit different metabolic waste products than normal cells. The differences between these metabolic products are so great that they can be detected by a dog’s keen sense of smell, even in the early stages of disease.
Early detection of cancers greatly improves a patient’s survival chances, and researchers hope that man’s best friend, the dog, can become an important tool in early screening.
A simple, cost-effective saliva test was developed to detect oral cancer, a breakthrough that would dramatically improve screening and lead to fewer people dying of the world’s sixth most common cancer.
Investigators in a study enrolled 100-120 patients with white lesions or growths in their mouths and tonsil areas, and looked for previously identified biomarkers to confirm the presence of oral cancer. By creating a simple saliva test which could identify the biomarker’s presence, they would know which patients need treatment and which ones could avoid needless and invasive biopsies.
The key challenge to tackle the issue of a poor survival rate linked to late detection of oral cancer is to develop strategies to identify and detect the disease when it is at a very early stage. The saliva-based test, as a noninvasive technique, greatly expand the abilities of clinicians to early screen for the cancerous lesions .
As commonly known in the biomedical community, genetic and epigenetic alterations are regarded as biomarkers for cancer detection, while some scientist looked for new candidates to indentify cancer, such as breath temperature, saliva, and smell.
Breath temperature test could identify lung cancer
A novel study, from the European Respiratory Society (ERS) International Congress in Munich,
shows that testing the temperature of breath could be a simple and noninvasive method to diagnose patients with lung cancer.
Researchers enrolled 82 people in the study who had been referred for a full diagnostic test after an x-ray suggested the presence of lung cancer. They found that patients with lung cancer had a higher breath temperature than those without. Also, They identified a cut-off value in the measurement of temperature, which they proved could identify lung cancer with a high level of accuracy.
The results suggest that lung cancer causes an increase in the exhaled temperature. This is a significant finding and could change the way clinicians currently diagnose the disease. If scientists able to refine a test to diagnose lung cancer by measuring breath temperature, they will improve the diagnostic process by providing patients with a simple and cheap test.
A new research confirms that tentacle-like structures called “invadopodia” plays a key role in the spread of cancer. This research, published in Cell Reports, shows that blocking formation of invadopodia can aid in stopping the spread of cancer.
There are an estimated 570,000 people living in the UK nowadays who have been diagnosed with breast cancer. Each year, around 50,000 women are diagnosed with breast cancer, and around 12,000 women die from this disease. With advances in medical research and care, cancer can often be treated with high success if detected early. However, after it spreads, cancer becomes much more difficult to treat.
Previous research has shown cancer cells are capable of producing “invadopodia,” a type of extension that cells use to probe and change their environment. However, their significance in the escape of cancer cells from the bloodstream has been unclear.
Novel research results confirmed the cancer cells formed invadopodia to reach out of the bloodstream and into the tissue of the surrounding organs. However, through genetic modification or drug treatment, the scientists were capable of blocking the factors needed for invadopodia to form. This effectively stopped all attempts for the cancer to spread.
Scientists suggest invadopodia may be an important new target for therapy, because it play a key role in the spread of cancer. If a drug can be developed to prevent invadopodia from forming, it could potentially stop dangerous spread.
Undoubtedly, there is an urgent need for medical agents to treat metastatic tumors. Pancreatic cancer, as one of the most aggressive types of cancer, cause 95% of the patients to die within 5 years after the diagnosis. To alter this situation, a scientist develops tumor therapeutic agents that might reduce this mortality rate. Currently, he has received a total of EUR 5 million to support preclinical and clinical tests of the agents.
The scientist currently schedule to utilize the funds acquired for the further development of candidate agents identified by other research team for the treatment of metastatic tumors. The candidate substances bind specifically to a so-called isoform of the surface molecule CD 44, and thus specifically interfere with central signaling paths of tumor growth, while other types of cells remain unaffected. What is seen is that New formation of blood vessels supplying the tumor and migration of cancer cells and their invasion into other organs are inhibited.
The research shows that this compounds do not only block the growth of primary tumors, but also prevent metastatic development and induce the regression of existing metastases. Although the scientist observed some remarkable effects in the previous animal tests, clinical studies carried out in future will show whether these positive effects will also occur in human patients without any side effects.
The target molecule (called CD44v6) of the above candidates plays a significant role for many type of tumors. It was discovered in the 1990s and its isoforms are increasingly considered significant factors for the spreading and formation of metastases. Blocking the receptor CD44v6 might open up opportunities for a wide-ranging application in tumor therapy.