Researchers from the Institute for Advanced Chemistry of Catalonia (IQAC) of Spanish National Research Council (CSIC) have developed a series of photosensitive molecule drugs that can be reversibly activated by external light, thus achieving a much more localized and controlled biological effect. This research, published in the Journal of Medicinal Chemistry, suggests that photopharmacology (drugs controlled by light) paves the path for highly specific therapies that could open new avenues for the treatment of diseases such as cancer.
One limitation of cancer drugs is that they often fail to fully differentiate between cancer cells and healthy cells. This lack of selectivity of current chemotherapy limits its therapeutic window, which decreases the effectiveness of the treatment and causes unwanted side effects.
"Photosensitive drugs, whose activity can be precisely controlled with external light in a reversible manner, can solve this problem, since they provide a great control of the site of action and for a desired time, thus decreasing the side effects and increasing their efficacy," explains Laia Josa Culleré, researcher from the Medicinal Chemistry and Synthesis group of IQAC, and lead author of this study.
Scientists at the University of East Anglia are a step closer to creating a new generation of light-activated cancer treatments. The futuristic-sounding treatment would work by switching on LED lights embedded close to a tumor, which would then activate biotherapeutic drugs.
These new treatments would be highly targeted and more effective than current state-of-the-art cancer immunotherapies.
New research published today in Nature Chemical Biology reveals the science behind this innovative idea. It shows how the UEA team have engineered antibody fragments—which not only "fuse" with their target but are also light activated.
It means that in future, immunotherapy treatments could be engineered to attack tumors more precisely than ever before.
Cancer Patients Who Don’t Respond to Immunotherapy Lack Crucial Immune Cells February 16, 2023
Introduction:
(EurekAlert) Immunotherapy has transformed cancer care. In advanced melanoma, for example, the most fatal form of skin cancer, the five-year survival rate has risen from less than 10% to more than 50% since immunotherapy was introduced in 2011. Still, only about half of melanoma patients respond to immunotherapy, and those who do not respond face a difficult future.
Researchers at Washington University School of Medicine in St. Louis have discovered that the difference between people who do and do not respond to immunotherapy may have to do with an immune cell known as CD5+ dendritic cells because they bear the protein CD5 on their outer surfaces. Their research showed that people with a variety of kinds of cancers, including melanoma, lived longer if they had more CD5+ dendritic cells in their tumors, and that mice that lacked CD5 on their dendritic cells were unable to respond well to immunotherapy.
The findings, published Feb. 17 in the journal Science, suggest that a supplementary therapy designed to increase the number or activity of CD5+ dendritic cells potentially could extend the lifesaving benefits of immunotherapy to more cancer patients.
“Immunotherapy has revolutionized the field of cancer therapy, but there are a lot of patients with cancer who don’t benefit from it,” said senior author Eynav Klechevsky, PhD, an assistant professor of pathology & immunology and a researcher at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “Part of the reason some people do not respond well to some forms of immunotherapy is because this population of dendritic cells is reduced dramatically. We’re developing some novel immune-based approaches to boost the activation of these CD5-expressing dendritic cells with a goal of helping more patients respond to immunotherapy.”
The immune system defends the body against cancer by activating immune cells known as T cells to recognize and kill tumor cells. In response, tumor cells manipulate the immune checkpoint system — a safeguard that prevents T cells from mistakenly attacking healthy cells — to hoodwink T cells into leaving them alone. Immune checkpoint blockade therapy works by thwarting tumor cells’ manipulations, thereby freeing T cells to recognize and destroy tumors. But even with therapy, some people’s T cells are unable to do their job effectively.
Building a new precision cancer treatment comes with no shortage of scientific challenges. Now, a group of University of Florida researchers have made a significant discovery in the effort to develop potent, highly targeted chemotherapies for breast and other cancers.
Scientists at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology have spent years developing antibody-drug conjugates, or ADCs, that combine a protective protein and a cancer-killing drug. Findings published recently in the Journal of Medicinal Chemistry detail the first time a particular type of cancer-killing "payload" has been used for ADC development.
The laboratory findings in leukemia cells are a key step in creating new medicinal payloads that can be altered and translated into ADCs to treat different types of cancer, the researchers said.
"We have shown we can precisely generate ADCs in a manner that is different than what anyone has done in the clinic. It's the ability to customize every single portion of ADCs in a pretty rapid fashion," said Andrew D. Steele, Ph.D., a postdoctoral research associate and co-first author of the paper.
Steele likens an ADC to a biological guided missile: The antibody is a targeting system that takes aim at the cancer. A potent, toxic compound is similar to a warhead, killing cancer cells by obliterating its DNA. A chemical linker acts like vital missile hardware, connecting the antibody and its chemical payload.
Building a new cancer-killing ADC posed several significant scientific hurdles, Steele said. Attaching payloads to antibodies in a controlled manner is quite challenging. Antibodies often have to be re-engineered for different types of cancers. Also, only six payloads are being used in federally approved ADCs. The current findings address all of those challenges, Steele said. The research was co-led by Ben Shen, Ph.D., a professor and director of the Natural Products Discovery Center, and professor Christoph Rader, Ph.D., both of The Wertheim UF Scripps Institute.
Estimates and Projections of the Global Economic Cost of 29 Cancers in 204 Countries and Territories From 2020 to 2050 by Simiao Chen, ScD; Zhong Cao, BE; Klaus Prettner, PhD5,6; et al
February 23 , 2023
Introduction:
(JAMA Network)
Key Points
Question What is the estimated economic cost and cost distribution of 29 cancers in 204 countries and territories from 2020 to 2050?
Findings In this decision analytical modeling study, the global economic cost of cancers from 2020 to 2050 was estimated to be $25.2 trillion (in international dollars at constant 2017 prices). The economic burden and the health burden were distributed unequally across countries, world regions, and country income groups.
Meaning
Results of this study suggest that global efforts to contain projected increases in the burden of cancers are warranted.
Abstract
Importance Cancers are a leading cause of mortality, accounting for nearly 10 million annual deaths worldwide, or 1 in 6 deaths. Cancers also negatively affect countries’ economic growth. However, the global economic cost of cancers and its worldwide distribution have yet to be studied.
Objective To estimate and project the economic cost of 29 cancers in 204 countries and territories.
caltrek’s comment: Having just completed reading The China Study by T. Colinn Campbell I wonder how much of these costs could be avoided by the simple expedient of a massive shift in developed countries to a Whole Foods, Plant Based approach to our diets. This is hampered by various cultural and political barriers. The political barriers being those put up by the meat and dairy industry to hamper governments from encouraging such a shift. Another example of the dysfunctional nature of capitalism as currently practiced.
An MUSC Hollings Cancer Center research team has created what team members believe to be among the first small molecules designed to stimulate immune cells to fight cancer. More importantly, these compounds inhibit a specific enzyme that hasn't been targeted with small molecules for the treatment of cancer.
Small molecules are, quite literally, small. They're hundreds of times smaller than monoclonal antibodies currently used in therapy, and they're also structurally much simpler. Because of their low molecular mass, they are much more likely to enter cells. Aspirin, for example, is a small molecule drug.
The team from the lab of Hollings researcher Patrick Woster, Ph.D., describes its findings in a paper in Chemical Science. Postdoctoral fellow Catherine Mills, Ph.D., said she wanted to look for potential new therapies for neuroblastoma, a serious and often fatal pediatric tumor.
The resulting research project served as the subject of her doctoral dissertation. Mills explained that the small molecule the team created has the potential to one day be an adjuvant therapy, a therapy that boosts the effects of another treatment, for other cancers in addition to neuroblastoma.
Michigan State University Research: DNA Repair Discovery Could Improve Biotechnology March 2, 2023
Introduction:
(EurekAlert) A team of researchers from Michigan State University’s College of Veterinary Medicine has made a discovery that may have implications for therapeutic gene editing strategies, cancer diagnostics and therapies and other advancements in biotechnology.
Kathy Meek, a professor in the College of Veterinary Medicine, and collaborators at Cambridge University and the National Institutes of Health have uncovered a previously unknown aspect of how DNA double-stranded breaks are repaired.
A large protein kinase called DNA-PK starts the DNA repair process; in their new report, two distinct DNA-PK protein complexes are characterized, each of which has a specific role in DNA repair that cannot be assumed by the other.
“It still gives me chills,” says Meek. “I don't think anyone would have predicted this.”
Pfizer buys Seagen for $43B, boosts access to cancer drugs
Source: AP
By TOM MURPHY and MICHELLE CHAPMAN an hour ago
Pfizer is spending about $43 billion to reach deeper into new cancer treatments that target tumor cells while sparing surrounding healthy tissue.
The pharmaceutical giant said Monday it will pay $229 in cash for each share of Seagen Inc. Pfizer then plans to let the biotech drug developer “continue innovating,” except with more resources than it would have alone, Pfizer Chairman and CEO Albert Bourla told analysts.
“We are not buying the golden eggs,” he said. “We are acquiring the goose that is laying the golden eggs.”
Bothell, Washington-based Seagen Inc. specializes in working with antibody-drug conjugate, or ADC, technology. Its key products use lab-made proteins called monoclonal antibodies that seek out cancer cells to help deliver a cancer-killing drug while sparing surrounding tissue.
Scientists at the National Institutes of Health and Massachusetts General Hospital in Boston have uncovered a potential new approach against liver cancer that could lead to the development of a new class of anticancer drugs. In a series of experiments in cells and mice, researchers found that an enzyme produced in liver cancer cells could convert a group of compounds into anticancer drugs, killing cells and reducing disease in animals.
The researchers suggest that this enzyme could become a potential target for the development of new drugs against liver cancers, and perhaps other cancers and diseases as well.
Researchers at University of California San Diego School of Medicine and Moores Cancer Center at UC San Diego Health have identified a strong association between the product of a gene expressed in most cancers, including the most common type of head and neck cancer, and elevated levels of white blood cells that produce antibodies within tumors.
The findings, published in the March 10, 2023 issue of PNAS Nexus, suggest a potential new target and approach for cancer immunotherapies that have thus far produced mixed results for certain head and neck cancers.
Telomerase reverse transcriptase (TERT) is an antigen abundantly produced in roughly 85% of tumor cells. Antigens are toxins or other substances that provoke an immune response against that substance. This is especially true with TERT in cancer patients.
But the effects of TERT expression on regulation of adaptive immunity within tumors is not understood. In the new study, co-senior study author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at UC San Diego Moores Cancer Center, and colleagues used RNA sequencing data from The Cancer Genome Atlas.
"Our data emerged through targeted computational reanalysis of The Cancer Genome Atlas, a valuable public tumor sequencing dataset, guided by core principles of immunology," said co-senior author Hannah Carter, Ph.D., associate professor at UC San Diego School of Medicine, said.
Specifically, Zanetti, Carter and their collaborators looked at 11 solid tumor types to investigate potential interactions between TERT expression and B and T cells that have infiltrated the tumor microenvironment.
B cells are immune response cells that produce antibodies to antigens, from bacteria and viruses to toxins. T cells are immune cells that target and destroy cells in the body that have been taken over by antigens or become cancerous. But B cells also present antigens to T cells triggering their activation in the process.
The researchers found a positive correlation between TERT expression and B and T cells in four cancer types, with the strongest association in head and neck squamous cell carcinoma, a condition that develops in the mucous membranes of the mouth, nose and throat.
They found that patients in which this association was found are linked to more favorable clinical outcomes. The findings, said Zanetti, suggest the de novo formation of lymphoid structures intra-tumor by B and T lymphocytes with TERT as potential connecting antigen.
Terminal leukaemia patients who were not responding to treatment now have hope for a cure, thanks to a new experimental pill called revumenib.
This drug has completely eliminated cancer in a third of the participants in a long-awaited clinical trial in the United States.
Although not all patients showed complete remission, scientists remain hopeful as the results indicate that the pill might pave the way to a cure for leukaemia in the future.
“We're incredibly hopeful by these results of patients that received this drug. This was their last chance,” said study co-author Dr Ghayas Issa, a leukaemia physician at the MD Anderson Cancer Center at the University of Texas.
“They have progressed on multiple lines of therapy and a fraction of them, about half, had disappearance of their leukaemia cells from their bone marrow,” he told Euronews Next.
Up to 50% of cancer-signaling proteins once believed to be immune to drug treatments due to a lack of targetable protein regions may actually be treatable, according to a new study from the Perelman School of Medicine at the University of Pennsylvania. The findings, published this month in Nature Communications, suggest there may be new opportunities to treat cancer with new or existing drugs.
Researchers, clinicians, and pharmacologists looking to identify new ways to treat medical conditions—from cancer to autoimmune diseases—often focus on protein pockets, areas within protein structures to which certain proteins or molecules can bind. While some pockets are easily identifiable within a protein structure, others are not. Those hidden pockets, referred to as cryptic pockets, can provide new opportunities for drugs to bind to. The more pockets scientists and clinicians have to target with drugs, the more opportunities they have to control disease.
The research team identified new pockets using a Penn-designed neural network, called PocketMiner, which is artificial intelligence that predicts where cryptic pockets are likely to form from a single protein structure and learns from itself. Using PocketMiner—which was trained on simulations run on the world's largest super computer—researchers simulated single protein structures and successfully predicted the locations of cryptic pockets in 35 cancer-related protein structures in thousands of areas of the body. These once-hidden targets, now identified, open up new approaches for potentially treating existing cancer.
What's more, while successfully predicting the cryptic pockets, the method scientists used in this study was much faster than previous simulation or machine-learning methods. The network allows researchers to nearly instantaneously decide if a protein is likely to have cryptic pockets before investing in more expensive simulations or experiments to pursue a predicted pocket further.
Immunotherapies have greatly improved the outcomes of many patients with melanoma. But there is still a need for new approaches for the subset of patients who do not respond well to this type of therapy. Moffitt Cancer Center researchers are looking at new targets to help inhibit tumor development and promote antitumor immunity, one being the STING signaling pathway. In a new article published in Nature Communications, a team of Moffitt and University of Miami Miller School of Medicine investigators demonstrate that targeting the STING pathway with a combination strategy results in improved antitumor activity.
The STING pathway is a key regulator of immune responses to viruses and bacteria and contributes to antitumor immunity. Inhibition of STING signaling is observed in several cancer cell lines, and expression of STING protein decreases as some cancer types progress, such as melanoma. These observations suggest that agonist drugs, or drugs that activate STING signaling within the tumor environment, may have antitumor effects.
Using Bacteria to Target Cancer Treatment March 28, 2023
Introduction:
(EurekAlert) When an outlet isn't designed for your plug, you need a plug adapter to get power to your devices.
Researchers at the University of Cincinnati have developed a similar approach to cancer treatment, using bacteria as the adapter to connect powerful radiation therapy to cancer cells. The research was recently published in Advanced Healthcare Materials.
Radionuclide therapy basics
The research focuses on delivering a cancer treatment called radionuclide therapy. Nalinikanth Kotagiri, PhD, corresponding author of the research, explained that radioactive material used in the treatment releases beta rays as it decays, destroying anything in its path.
This treatment is typically delivered in a targeted way, with the cancer-killing radiation binding to the cancer cells through receptors on the cell surface to spare as many surrounding healthy cells as possible.
“Every cancer type has its own unique epitopes, or receptors, that are expressed on its surface,” said Kotagiri, a University of Cincinnati Cancer Center researcher and associate professor at UC's James L. Winkle College of Pharmacy. “With that information, you can deliver a drug or radiation, using molecules such as antibodies and peptides, only to the cancer cells where it’s supposed to go, and not anywhere else like vital organ
In recent years, innovative cancer drugs that target specific molecular drivers of the disease have been embraced as the treatment of choice for many types of cancer. But despite significant advances, there is still a lack of understanding about how the complex interactions between a tumor and its surrounding environment in the body affect cancer progression. This problem has become a well-known roadblock in making novel treatments effective for more people.
Ankur Singh, professor in the George W. Woodruff School of Mechanical Engineering and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, has led an international team of researchers in the development of a promising breakthrough for targeted cancer therapies.
The team bioengineered a synthetic tumor model to understand and then demonstrate how the tumor microenvironment impacts the effectiveness of targeted therapies for a specific type of lymphoma called Activated B Cell-like Diffuse Large B cell lymphoma (ABC-DLBCL). Their synthetic tumor model could change the game for designing and testing personalized cancer therapies. The research paper, which features an interdisciplinary team from institutions across the U.S. and around the world, was published in the journal Nature Materials.
Researchers at the Washington University School of Medicine, St. Louis, have discovered a potential new target for cancer immunotherapy in transposable elements (TEs), short segments of DNA that can move around the genome.
In the paper, "Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements" published in Nature Genetics, researchers used the Cancer Genome Atlas (TCGA), a database of more than 20,000 cancer samples covering 33 distinct cancer types and and 675 cancer cell lines.
The paper focuses on transposable elements (TEs) that exist in the human genome but are often dormant. These are, as the name implies, segments of DNA that can insert themselves into other genes. The classic example is a retrovirus that incorporates some of its genetic code in the genome of a host. The genome is prepared for this sort of intrusion, and continued replication and insertion is typically "turned off."
When cancers develop, they do so without much of the normal genetic failsafes in place, as they often originate from cells that have damaged DNA to begin with. In replicating, cancer allows these dormant TEs to regain their transposable ability within cancer cells and, according to the study, "drive expression of atypical transcripts that, at times, can be both highly expressed and widely shared across tumor samples."
Global breakthrough treating childhood cancer with artificial intelligence
8:45pm Mar 31, 2023
Researchers have found a way to make digital models of tumours to help find new treatments for childhood cancers.
A team of doctors from Clayton's Hudson Institute has collected more than 300 samples of children's tumour cells to develop a digital collection of tumours, called the Childhood Cancer Model Atlas.
Each tumour is grown in a lab and then turned into an accurate model online.
Researchers then test the digital tumour with artificial intelligence, allowing them to trial hundreds of drugs and treatments on a child's tumour without having to test the child themselves.
"Because we've done this for thousands of patients we've been able to generate terabytes, tens of terabytes of data," Professor Ron Firestein said. "That allows us to use a very powerful artificial intelligence method to predict which drug will work in what specific type of children's cancer."
Understanding and Fighting Metastatic Cancer April 5, 2023
Introduction:
(Eurekalert) “There won’t be a miracle cure for cancer,” says Thomas Brabletz. “A multi-faceted approach has to be taken to fighting cancer, which means that the most successful treatment strategy is likely to involve an intelligent combination of drugs, often tailored to the individual patient’s needs, that target various weaknesses.” Thomas Brabletz, a renowned cancer researcher, hopes to pinpoint these weaknesses, and is focusing on a relentless opponent that is still almost invariably fatal, even today and in spite of the major advancements made over recent years: metastatic cancer. He is also exploring why some types of cancer develop resistance to treatment and lead to cancer recurring after initially successful treatment.
Thomas Brabletz is Chair of Experimental Medicine I (Molecular Pathogenesis Research) and the Vice Dean for research at the Faculty of Medicine. Ever since he was a student, he has been interested in the biological mechanisms triggering cancer. He chose to focus on molecular pathology and completed his postdoctoral habilitation in this subject at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) in 1998. In 2007, he was appointed professor of molecular oncology at the University of Freiburg, before returning to Erlangen in 2014. Brabletz, who is also a qualified doctor, is one of the leading cancer researchers worldwide; he has published 180 peer reviewed publications and presented his research as a speaker at international conferences and symposia more than 270 times.
Migrating cancer stem cells
Brabletz was the first researcher to identify migrating cancer stem cells as the cause of metastasis and treatment resistance, roughly 20 years ago. “Until then, researchers believed that metastasis was predominantly driven by an irreversible accumulation of mutations,” he explains. Normal stem cells have a decisive role to play in embryonic development and tissue homeostasis. They allow any number of different types of tissues and organs to be formed from an original small cluster of cells. The important factor in this process is that epithelial cells are capable of converting into mesenchymal cells. These mesenchymal cells then migrate to pre-determined locations and develop there into tissue complexes.
Cancer cells are notorious for evading detection by the body’s immune system, making them difficult to treat. But a promising new type of genetically engineered T-cell that can effectively destroy solid cancer tumors may be just what the doctor ordered.
Killer T-cells are an important part of the immune response. They are the body’s security guards, actively patroling for things that don’t belong, such as infections and other diseases. Killer T-cells possess surface receptors that recognize and latch on to foreign invaders and abnormal cells, destroying them.
Cancer cells can evade detection by killer T-cells, making them difficult to destroy. But there is a way our body’s T-cells can be “taught” to recognize and attack cancer cells. One approach is to use chimeric antigen receptor (CAR) T-cells, genetically engineered cells with a new receptor that allows them to bind to and kill cancer cells.
