Researchers have developed an automated platform that they've used to screen thousands of drugs and identify those that can be used to interrupt the spread of melanoma, one of which they successfully trialed on mice. The approach could help identify promising drugs to treat metastatic cancers.
Metastatic cancers, particularly melanoma, continue to present a challenge because each tumor may have a unique microenvironment and respond differently to treatment. A particularly aggressive form of cancer, once melanoma has spread, its survival rate is low.
A feature of the metastatic process is the formation of invadopodia by tumor cells, specialized protrusions whose function is to degrade the extracellular matrix so that the cells can enter – or invade – new environments. Identifying drugs that target invadopodia is crucial to effectively preventing cancer spread, but currently, the ability to screen for these drugs is lacking.
To identify potential therapeutic targets and preclinical drug candidates for the treatment of ovarian cancer, researchers led by Tan Li from the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences have developed novel small molecule inhibitors of CPSF3, a key module of the cleavage and polyadenylation specificity factor (CPSF) complex that catalyzes pre-mRNA splicing and regulates transcription termination.
This work was published in Science Advances on Nov. 22.
Ovarian cancer is the deadliest gynecological cancer and is often diagnosed at a late stage. In treating ovarian cancer, surgery and systemic chemotherapy can modestly improve the survival rate, while targeted therapies with PARP inhibitors are effective in a limited number of ovarian cancer patients.
Ovarian cancer is often characterized by frequent copy number alterations and dysregulated gene expression, making transcription a potential point of attack for drug therapies.
Common local anesthetic may be effective against head and neck cancers
By Paul McClure
November 26, 2023
https://newatlas.com/medical/lidocaine- ... k-cancers/
A new study has uncovered how the commonly used local anesthetic drug, lidocaine, activates bitter taste receptors to exert an anti-cancer effect in head and neck cancers. Given its low cost and ready availability, the drug could easily be incorporated into the treatment of patients with this challenging form of cancer.
Anyone who’s had a cut sutured up or a dental procedure such as a filling will probably be familiar with lidocaine (also known as lignocaine). While it’s known how the local anesthetic drug exerts its pain-inhibiting effects, it’s been suggested that lidocaine also has a beneficial effect on cancer patients, although how is not fully understood.
Now, a study led by researchers at the University of Pennsylvania School of Medicine has solved a long-standing mystery of how lidocaine causes the death of certain cancer cells.
“We’ve been following this line of research for years but were surprised to find that lidocaine targets the one receptor that happened to be mostly highly expressed across cancers,” said Robert Lee, a corresponding author of the study.
Immunotherapy drug proves promising for deadly small cell lung cancer
By Paul McClure
November 26, 2023
https://newatlas.com/medical/tarlatamab ... ng-cancer/
Researchers have published the results of a clinical trial evaluating the efficacy of an immunotherapy drug in treating a particularly aggressive form of lung cancer. Tarlatamab produced promising results, demonstrating antitumor activity and improving survival rates in patients for whom previous treatments hadn’t worked.
Like all cancers, small cell lung cancer (SCLC) begins at the cellular level and causes cancerous cells to reproduce rapidly and uncontrollably. However, its rapid growth makes SCLC the most aggressive form of lung cancer, and not many people with it are still alive five years after diagnosis, making identifying an effective treatment all the more important.
A Phase 2 clinical trial led by researchers at the Karl Landsteiner Private University of Health Sciences, Austria, evaluated an immunotherapy drug, tarlatamab, for antitumor activity and survival in patients with SCLC who’d previously received two lines of treatment.
Greater Adherence to Lifestyle Recommendations Associated with Lower Cancer Risk November 27, 2023
Introduction:
(Eurekalert) Greater adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations — which encourage a healthy lifestyle — is associated with a lower risk of all cancers combined and some individual cancers such as breast cancer. The findings are published in BMC Medicine.
The 2018 WCRF/AICR cancer prevention recommendations aim to reduce the risk of cancer by encouraging individuals to maintain a healthy weight, be physically active, and eat a diet rich in wholegrains, vegetables, fruit, and beans, but low in highly processed foods, red and processed meat, sugar-sweetened drinks, and alcohol.
John Mathers and colleagues investigated the relationship between adherence to the WCRF/AICR recommendations and cancer risk by analysing UK Biobank data for 94,778 British adults, who were 56 years old on average. The researchers used self-reported dietary and physical activity data — in addition to participants’ body mass index and waist circumference measurements — to score participants’ adherence to the recommendations out of a maximum score of 7 points. They used cancer registry data to calculate the incidence of new cancers that developed over an average period of 8 years. They accounted for age, sex, socioeconomic deprivation, ethnicity, and smoking status in their analyses. The average recommendation adherence score was 3.8 points and 7,296 participants (8%) developed cancer during the study period.
The authors found that greater adherence to the WCRF/AICR recommendations was associated with a lower risk of all cancers combined, with each 1-point increase in recommendation adherence score associated with a 7% lower risk. Compared to those with an adherence scores of 3.5 points or less, those with a score of 4.5 points or above had a 16% lower risk of all cancers combined. They also found that each 1-point increase in adherence score was associated with a 10% lower risk of breast cancer, a 10% lower risk of colorectal cancer, an 18% lower risk of kidney cancer, a 16% lower risk of oesophageal cancer, a 22% lower risk of liver cancer, a 24% lower risk of ovarian cancer, and a 30% lower risk of gallbladder cancer.
A breakthrough in the understanding of the relationship between a naturally occurring enzyme and the liver cancer drug sorafenib could improve the effectiveness of the drug, which currently prolongs the life of liver cancer patients for only two to three months. A study of the relationship between the enzyme DDX5, liver cancer sorafenib, published in the journal Cell Death & Disease, points to the potential for a more effective therapy that combines existing anti-cancer drugs with treatments that spur production of this enzyme.
"If we can find a way to continuously express DDX5 in the liver during treatment, then sorafenib and other multi-tyrosine kinase inhibitors have much better anti-tumor efficacy," said Ourania Andrisani, lead researcher and Distinguished Professor of Basic Medical Sciences in the College of Veterinary Medicine at Purdue University. "This is a foundational discovery, and from this, we can think of new ways to develop effective therapies for liver cancer."
In what has already been tagged as a “game-changer” for cancer treatment, the potent once-a-day tablet known as divarasib has continued to impress at Phase 1b trial stage, outperforming not just current therapies but its previous trial results.
Following on from a standalone clinical trial earlier this year, divarasib has now been combined with the existing targeted immunotherapy drug cetuximab, and has delivered a 62.5% positive outcome for people with advanced or metastatic colorectal cancer (CRC) linked to the KRAS G12C gene mutation.
In the first trial, at the Peter MacCallum Cancer Center in Australia, CRC patients receiving just divarasib had a 35.9% positive response rate, which was considered extremely promising.
KRAS is a key protein that regulates how cancer cells behave. For cancer patients with the KRAS G12C gene mutation, their cancer cells are far more likely to divide uncontrollably and form tumors, making the disease very challenging to treat with existing medication. As such, even though it affects around 4% of CRC patients, it has a poor prognosis.
A team from Children's Medical Research Institute has discovered a new way to impair cancer cell growth, which could lead to the development of a new class of cancer therapeutics with minimal side-effects on normal cells.
Professor Hilda Pickett, who leads CMRI's Telomere Length Regulation Unit, said this was an exciting development for their team.
"This project builds on over a decade of work by my team and our collaborators to develop antiproliferative agents that target telomeres. The results are promising and have future potential to improve long term health outcomes for all types of cancer," says Pickett.
Lymphatic fluid from surgical drains, which is usually tossed in the trash, is a treasure in the hands of University of Pittsburgh and Washington University School of Medicine in St. Louis researchers who found that this liquid could inform more precise treatments for patients with head and neck cancer caused by human papillomavirus (HPV).
The new study, published in Clinical Cancer Research, shows for the first time that HPV DNA in lymphatic fluid collected after surgery is a powerful biomarker that could predict risk of cancer recurrence and help clinicians decide whether to ramp up adjuvant therapies or safely de-escalate treatment for patients with HPV-positive head and neck cancer.
"Over the last decade, there has been emerging interest in liquid biopsy to pick up cancer recurrences after treatment," said senior author José P. Zevallos, M.D., M.P.H., professor and Eugene N. Myers, chair of the Department of Otolaryngology at the Pitt School of Medicine and UPMC Hillman Cancer Center. "Our goal was to bring liquid biopsy into the curative pathway for head and neck cancer so that we can use it not just to find recurrences but also to help make treatment decisions."
Head and neck cancer once almost exclusively affected heavy drinkers and smokers, but the landscape of this disease has changed dramatically because of HPV, according to Zevallos. HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) has now surpassed cervical cancer as the most common HPV-related malignancy, and incidences are rising rapidly worldwide.
Monitoring cancer cells effectively can help physicians with treatment and management, thus reducing cancer-related mortality. Can non-invasive technologies pave the way for improved monitoring to reduce cancer mortality rates? Diagnostic platforms that non-invasively measure the electrical properties of cancer cells offer promise in the early detection of cancer drug resistance and metastasis.
Research has shown that it is possible to understand a cancer type and its drug resistance status from cellular permittivity and conductivity data. In fact, there is an increasing demand for analytical methods that can rapidly measure a cell's electrical properties.
Hodgkin lymphoma prognosis, biology tracked with circulating tumor DNA
by Stanford University Medical Center
A Stanford Medicine-led, international study of hundreds of samples from patients with Hodgkin lymphoma has shown that levels of tumor DNA circulating in their blood can identify who is responding well to treatment and others who are likely to experience a disease recurrence—potentially letting some patients who are predicted to have favorable outcomes forgo lengthy treatment.
Surprisingly, the study also revealed that Hodgkin lymphoma, a cancer of the lymph nodes, can be divided into two groups, each with distinct genetic changes and slightly different prognoses. These changes hint at weaknesses in the cancer's growth mechanisms that could be targeted by new, less toxic therapies.
Monitoring cancer cells effectively can help physicians with treatment and management, thus reducing cancer-related mortality. Can non-invasive technologies pave the way for improved monitoring to reduce cancer mortality rates? Diagnostic platforms that non-invasively measure the electrical properties of cancer cells offer promise in the early detection of cancer drug resistance and metastasis.
Research has shown that it is possible to understand a cancer type and its drug resistance status from cellular permittivity and conductivity data. In fact, there is an increasing demand for analytical methods that can rapidly measure a cell's electrical properties.
Hodgkin lymphoma prognosis, biology tracked with circulating tumor DNA
by Stanford University Medical Center
A Stanford Medicine-led, international study of hundreds of samples from patients with Hodgkin lymphoma has shown that levels of tumor DNA circulating in their blood can identify who is responding well to treatment and others who are likely to experience a disease recurrence—potentially letting some patients who are predicted to have favorable outcomes forgo lengthy treatment.
Surprisingly, the study also revealed that Hodgkin lymphoma, a cancer of the lymph nodes, can be divided into two groups, each with distinct genetic changes and slightly different prognoses. These changes hint at weaknesses in the cancer's growth mechanisms that could be targeted by new, less toxic therapies.
I am still a great believer in the GIGO principle. GIGO as in Garbage In, Garbage Out. I think that this still holds true for AI. It still does not seem capable of understanding mistakes made in its programming and in data submitted to it. More precise measuring devices generating relatively reliable data sets can thus make for a very powerful basis for further advancement in most any field, including cancer research and diagnosis.
Boosting Immunotherapy in Non-responsive Cancer Cells December 11, 2023
Introduction:
(Eurekalert) Cancer immunotherapy primes a patient's immune system to better find and destroy cancer cells, improving upon the body's natural ability to fight tumours. Contemporary immunotherapy approaches aim to stimulate immune cells called T cells to target tumours. In this process, the production and functioning of a cytokine (a small signalling protein) known as Interferon-gamma (IFN-γ) are essential for the immune system to eliminate tumours effectively. These approaches affect fewer normal cells when compared to chemotherapy or radiation. However, they are either very expensive or less efficient.
In a new study, researchers at the Indian Institute of Science (IISc) tried to understand how different types of cancer cells respond to IFN-γ activation. They found that only some types of cancer cells respond well to IFN-γ activation, while others don't. They also suggest some approaches that can be used to make these non-responsive cancer cells better respond to immunotherapy. The study was published in Frontiers in Immunology.
"IFN-γ is produced by immune cells such as T cells or natural killer cells. It binds to tumours, and induces apoptosis [cell death]," explains Avik Chattopadhyay, first author and PhD student at the Department of Biochemistry, IISc. "Reports in the literature have shown earlier that if there are lower amounts of IFN-γ or defects in its signalling, then the tumours don't respond well to the immunotherapy processes."
In the current study, when the team first treated cancer cells in the lab with IFN-γ, they found that the colour of the cell growth medium changed to yellow, indicating that the cells were releasing acidic byproducts such as lactic acid. This led the team to dig deeper into the role of these byproducts. They found that the higher amounts of lactic acid produced in the cell culture medium was due to increased glycolysis, a series of chemical reactions that extracts energy from glucose.
The team found that cancer cell lines derived from the liver and the kidney showed increased production of nitric oxide (NO) and lactic acid upon IFN-γ activation. This, in turn, increased the production of toxic reactive oxygen species (ROS) leading to oxidative damage, which eventually kills the cancer cells.
Researchers Discover Key to Epithelial Cell Growth December 21, 2023
Introduction:
(Eurekalert) Australian researchers have discovered a new way that epithelial cells, which form layers in organs like the skin and stomach, attach to one another, and how they perceive growth signals at these attachments, helping them form tissues of the right size and shape.
Epithelial cells cover the surfaces of most organs in the body and must adhere to each other to form both a protective and permeable barrier. They are exquisitely designed to both be tightly sealed against pathogens like bacteria, and to also allow the transport of salts, fluids, and nutrients.
Researchers, led by Professor Kieran Harvey and Dr Benjamin Kroeger, at the Monash University Biomedicine Discovery Institute in Melbourne have discovered a new way by which epithelial cells adhere to each other in the vinegar fly, Drosophila. The study is published today in the journal, Developmental Cell.
Previous work from Professor Harvey and others led to the discovery of an important organ growth control pathway, called Hippo. First discovered in Drosophila, the Hippo pathway does effectively the same job in mammals and controls the size of different organs such as the liver and heart. The Hippo pathway is also important for human diseases as it is mutated in multiple epithelial cancers. The new study provides further insights into how Hippo signalling is coordinated in growing tissues.
In the present study, the researchers made the important discovery of a new subcellular adhesion site that helps epithelial cells adhere to one another – termed by the researchers as “basal spot junctions”. They showed that basal spot junctions not only helped cells adhere to one another but were important for regulating Hippo signalling. “Our discovery of basal spot junctions in epithelial tissues has given us new insights into how epithelial cells adhere to each other and how epithelial tissues grow to the right size and shape,” Professor Harvey said.
A drug screening system that models cancers using lab-grown tissues called organoids has helped uncover a promising target for future pancreatic cancer treatments, according to a new study from researchers at Weill Cornell Medicine.
In the study, published Dec. 26 in Cell Stem Cell, the scientists tested more than 6,000 compounds on their pancreatic tumor organoids, which contain a common pancreatic cancer-driving mutation. They identified one compound—an existing heart drug called perhexiline maleate—that powerfully suppresses the organoids' growth.
Researchers have found that inexperienced doctors performing AI-assisted colonoscopies significantly improved their detection of polyps. Using AI with this diagnostic tool could lower the chances of missing these potential precursors to colorectal cancer.
The addition of AI has led to the enhancement of several medical diagnostic tools, including mammography, ultrasound, and MRI. Now it’s colonoscopy’s turn to get a computer-aided upgrade.
Colonoscopy, the insertion of an endoscope into the colon to examine its interior walls, reduces the incidence of colorectal cancer-related death by detecting and removing premalignant polyps, otherwise known as adenomas. However, as a diagnostic tool, colonoscopy can be imperfect; up to 26% of adenomas and 9% of advanced adenomas can be missed, increasing the risk of adverse outcomes and mortality. Reasons adenomas are missed include flat morphology, poor bowel preparation, and insufficient endoscopist experience.
