As described in the March 7 issue of Nature Communications, investigators used a two-drug combination to achieve chemotherapy's goal: to make cancer cells self-destruct via the biological process known as apoptosis, often referred to as programmed cell death. The treatment worked against human cancer cell lines that resisted apoptosis despite exposure to different types of chemotherapy, and also against apoptosis-resistant human tumors implanted in mice (i.e., xenograft mouse models).
"Targeted therapies that home in on specific genetic vulnerabilities of cancers have vastly improved treatment in recent years, but not everyone has benefited," said Evripidis Gavathiotis, Ph.D., professor of biochemistry and of medicine at Einstein, co-leader of the Cancer Therapeutics Program at the NCI-designated Albert Einstein Cancer Center, and corresponding author on the paper. "We need new, broadly active therapies that can attack a range of cancers while causing fewer side effects than current treatments, and we hope our new therapeutic strategy will prove to be a viable option."
A collaborative study led by the Monash Biomedicine Discovery Institute (BDI) has discovered a new immune checkpoint that may be exploited for cancer therapy.
The study shows that by inhibiting the protein tyrosine phosphatase PTP1B in T cells, the body's immune response to cancer can be mobilized, helping to repress tumor growth.
T cells are an essential part of the body's immune system, helping not only to kill invading pathogens, such as viruses but also cancer cells. However, this study has shown that using a new drug candidate, the abundance of PTP1B in T cells that infiltrate tumors is increased, thereby restraining the ability of T cells to attack tumor cells and combat cancer. These findings have identified PTP1B as an intracellular brake, or checkpoint, reminiscent of the cell surface checkpoint PD-1—the blockade of which has revolutionized cancer therapy.
The findings are published in the prestigious journal Cancer Discovery.
Using mice, scientists from Monash BDI, in conjunction with colleagues at the Peter MacCallum Cancer Center in Melbourne and Cold Spring Harbor Laboratory in New York, found that by inhibiting PTP1B, using an early-stage injectable drug candidate that has previously been shown to be safe and well-tolerated in humans, the cancer-fighting ability of T cells is enhanced, repressing tumor growth.
Treating cancer and other diseases with laser light is not currently considered routine in the clinical setting, but new approaches using nanoparticles show some promise in improving existing techniques.
One technique, known as photothermal therapy (PTT), converts laser light into heat that can target and kill tumor cells. Another technique, photodynamic therapy (PDT), uses laser light to generate reactive oxygen species (ROS), such as hydroxyl radicals, singlet oxygen, superoxide radicals, and hydrogen peroxide, which can wreak devastation on tumor cells.
In Applied Physics Reviews, a multinational team of researchers reviews the current status of the field of nanoparticle-enhanced PDT and PTT and focuses on combining the two techniques to achieve the highest level of treatment efficiency.
By combining PTT or PDT with nanomaterials, investigators have been able to apply these types of phototherapies while also delivering drugs to sites in the body that are otherwise inaccessible. It is also possible to combine PTT and PDT into a single treatment, creating an even more powerful treatment method.
In a study published in Cell Reports Medicine, a group of Chinese scientists revealed the oncometabolite role of progesterone in advanced prostate cancer and strategies to eliminate its oncogenic effect as an aspect of prostate cancer treatment.
Androgen sustains the development of prostate cancer. Although androgen deprivation therapy and abiraterone eliminate the generation of androgen, disease progression is still inevitable.
In this study, a research team led by Li Zhenfei of the CAS Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences investigated alteration in the metabolomics of abiraterone-resistant patients and found that one metabolite—progesterone—increased significantly. Transient treatment with high doses of progesterone will activate multiple pathways to promote the proliferation of cancer cells. Long-term treatment with progesterone at a low dosage will increase the expression of GATA2, resulting in an irreversible alteration in the transcriptome that promotes disease progression.
They also investigated the metabolic pathway of progesterone. They identified the enzyme 3bHSD1 as a potential therapeutic target for eliminating the generation of progesterone. Specifically, they discovered that biochanin-A, an isoflavone rich in soy and other foods, is a 3bHSD1 inhibitor and suppresses prostate cancer development.
Based on the oncogenic effects of progesterone, plasma progesterone levels were found to be negatively correlated with the duration of abiraterone treatment. Thus, progesterone might be a potential predictive biomarker for abiraterone response and related clinical research is in progress.
Tumors can use an enzyme called ART1 to thwart antitumor immune cells, making the enzyme a promising new target for immunity-boosting cancer treatments, according to a study from researchers at Weill Cornell Medicine and Albert Einstein College of Medicine.
In the study, published Mar. 16 in Science Translational Medicine, the researchers found strong evidence that ART1, when expressed on tumor cells, can modify a receptor on tumor-fighting immune cells in a way that triggers the death of these immune cells. In animal models of cancer, blocking ART1 increased the presence of the tumor-fighting immune cells within tumors and slowed or stopped tumor growth.
"These findings should allow us to add to our medicinal toolkit for enhancing the antitumor immune response, to benefit cancer patients," said study co-corresponding author Dr. Timothy McGraw, professor of biochemistry and of biochemistry in cardiothoracic surgery and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
Mount Sinai scientists have developed a new technology allowing them to link specific genes to complex tumor characteristics at a scale and resolution not previously possible. The results could lead to new approaches for targeting anti-cancer drugs.
The technology, called Perturb-map, uses a novel genetic barcode system to mark cancer cells with different gene modifications and image the cancer cells, as well as neighboring non-cancer cells, within tissue. Using this approach, the researchers were able to identify specific genes controlling lung tumor growth, immune composition, and even response to immunotherapy, according to the study, published in the March issue of Cell.
A study published in the journal Nature Cancer, carried out within the Cancer Program at the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar) by the Cancer Stem Cells and Metastasis Dynamics Laboratory, led by Dr. Toni Celià-Terrassa, and the Laboratory of Molecular Cancer Therapy, coordinated by Dr. Joan Albanell, with the participation of international centers, has discovered an approach that radically increases the success of immunotherapy in one of the most aggressive types of tumors, triple-negative breast cancer. This subtype, although accounting for only 15% of cases, is one of the most rapidly progressing and affects younger patients. In this work, researchers found that tumor stem cells are the main cause of immunotherapy resistance in this subtype of breast cancer. The reason is that these cells are invisible to the immune system, making immunotherapy ineffective. In addition, the study offers a promising solution to this situation by using a new therapeutic approach in preclinical models that makes cancer stem cells visible to the immune system so that it can then eliminate the tumor.
Columbia Engineering researchers report that they have developed a "cloaking" system that temporarily hides therapeutic bacteria from immune systems, enabling them to more effectively deliver drugs to tumors and kill cancer cells in mice. By manipulating the microbes' DNA, they programmed gene circuits that control the bacteria surface, building a molecular "cloak'' that encapsulates the bacteria.
"What's really exciting about this work is that we are able to dynamically control the system," said Tal Danino, associate professor of biomedical engineering, who co-led the study in collaboration with Kam Leong, Samuel H. Sheng Professor of Biomedical Engineering. "We can regulate the time that bacteria survive in human blood, and increase the maximum tolerable dose of bacteria. We also showed our system opens up a new bacteria delivery strategy in which we can inject bacteria to one accessible tumor, and have them controllably migrate to distal tumors such as metastases, cancer cells that spread to other parts of the body."
For the study published today by Nature Biotechnology, the researchers focused on capsular polysaccharides (CAP), sugar polymers that coat bacterial surfaces. In nature, CAP helps many bacteria to protect themselves from attacks including immune systems. "We hijacked the CAP system of a probiotic E. coli strain Nissle 1917," said Tetsuhiro Harimoto, a Ph.D. student in Danino's lab who is the study's co-lead author. "With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch."
New research from Mayo Clinic's Center for Individualized Medicine finds that patients with ASXL1-mutant chronic myelomonocytic leukemia—an uncommon type of cancer of the bone marrow—have distinctive epigenetic changes that can activate harmful genes and cause the cancer to grow faster. The ASXL1 genetic mutation also can transform the disease into the more aggressive acute myeloid leukemia.
The study, published in Nature Communications, helps to clarify a potential therapeutic strategy and adds to the knowledge of ASXL1 gene expression.
Epigenetics refers to chemical modifications of a cell's genetic material that control how genes are expressed and affect the interpretation of the DNA code. Research shows epigenetics play a critical role in the development and
A multicenter research team co-led by The University of Texas MD Anderson Cancer Center developed the first drug to treat the uncontrolled secretion of mucins in the airways, which causes potentially life-threatening symptoms in millions of Americans with asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), as well as lung disease resulting from cancer and cancer treatment. The study was published today in Nature.
"Mucus is a significant problem in pulmonary medicine, because in people with these common lung diseases, thick mucus can block the airways and cause symptoms ranging from a mild cough to very serious decreases in lung function," said Burton Dickey, M.D., professor of Pulmonary Medicine and co-corresponding author of the study. "Most drugs for these conditions work to reduce inflammation or expand the airways to help people breathe better, but mucus is the most serious issue. Our research has created the first drug that would stop the secretion of mucins in its tracks."
(EurekAlert) A new clinical trial at the University of Cincinnati is studying the effectiveness of a new two-pronged immunotherapy treatment procedure to treat the most aggressive and deadly type of brain tumors, called glioblastomas. Originating from healthy brain cells, glioblastomas can form in any area of the brain.
Mario Zuccarello, MD, said surgeons can remove the visible tumor as long as it does not affect areas of the brain that affect function, but microscopic particles of the tissue remain behind no matter how precise the surgeon is. Because of this, treatment typically includes a combination of surgery, radiation and chemotherapy. Even with advances in the field over the past few decades, he said the tumors return about nine months after treatment in most cases, and most patients do not survive past 12-15 months after original diagnosis.
“Unfortunately the end result, which is an inability to cure the patient, has remained,” said Zuccarello, the John M. Tew MD endowed chair in neurosurgical oncology at the UC College of Medicine, director of the UC Health Brain Tumor Center and a UC Cancer Center member. “We try to prolong life as much as possible, but the quality of life is a big problem, because these patients are not only subjected to surgical procedures, and sometimes repeated surgical procedures, but also chemotherapy and radiation.”
As researchers continue to discover new receptors and pathways that help the tumors grow, Zuccarello said clinical trials to test new drug targets are essential to move closer to a day where there is a cure for patients with glioblastomas.
UC is currently recruiting for the new trial, operated in collaboration with the Dana-Farber Cancer Institute, a teaching affiliate of Harvard Medical Schoo
New research has found that the weakened immune systems of blood cancer patients can improve after they receive a third COVID-19 vaccination.
Patients with lymphoma have defects in their immunity system that restrict its response to vaccination. Despite this, this new study found improvements in antibody and T-Cell responses after a third vaccine dose, except in patients who had recently received a certain antibody treatment for their cancer.
The study was funded by the Blood Cancer UK Vaccine Research Collaborative and has been published in the journal Nature Cancer.
"Despite the gradual lifting of COVID-19 restrictions worldwide, a cloud continues to hang over immunosuppressed patients, who may not develop protective immune responses after vaccination," explained Dr. Sean Lim, Associate Professor and Honorary Consultant in Haematological Oncology at the University of Southampton, who led the research. "In particular, individuals with hematological malignancies are at greater risk of severe COVID-19 disease even if they have been vaccinated," she continued.
University of Notre Dame researchers have discovered another way tumor cells transfer genetic material to other cells in their microenvironment, causing cancer to spread.
In their latest study, published in Cell Reports, Crislyn D'Souza-Schorey, the Morris Pollard Professor in the Department of Biological Sciences, and collaborators discovered that DNA "cargo" is transported in small informational sacs called extracellular microvesicles. Their study is a continuation of work her lab has undertaken to further understand the sharing of information between cells.
"We've shown that DNA present in these microvesicles is related to metastasis, so now we have a great platform to assess for genetic aberrations," said D'Souza-Schorey, who is also affiliated with the Berthiaume Institute for Precision Health, the Boler-Parseghian Center for Rare and Neglected Diseases and the Harper Cancer Research Institute.
Cancer cells, unlike normal cells, are often filled with cytosolic DNA, which is DNA found in the jelly-like fluid outside of the cell's nucleus. This DNA can be derived from multiple sources, but recent evidence suggests that chromosomal instability is a primary source of cytosolic DNA in tumor cells.
The research team used a cell model from a male cancer patient to show how Y-chromosomal DNA—present in the cytosol due to chromosomal instability—is carried by extracellular vesicles and transferred to a female mammary epithelial cell line.
A new approach from Penn Medicine researchers could cut the time it takes to alter patients' immune cells for infusion back into the body to find and attack cancer. The cell manufacturing process for this type of immunotherapy that was pioneered at Penn—CAR T cell therapy—typically takes 9 to 14 days. In a pre-clinical study published in Nature Biomedical Engineering, a team in the Perelman School of Medicine at the University of Pennsylvania abbreviated this process and generated functional CAR T cells with enhanced anti-tumor potency in just 24 hours.
These results demonstrate the potential for a vast reduction in the time, materials, and labor required to generate CAR T cells, which could be especially beneficial in patients with rapidly progressive disease and in resource-poor healthcare environments. The study was led by Center for Cellular Immunotherapies researchers Michael C. Milone, MD, Ph.D., an associate professor of Pathology and Laboratory Medicine and Saba Ghassemi, Ph.D., a research assistant professor of Pathology and Laboratory Medicine.
Kathleen DelGiorno, assistant professor of cell and developmental biology, her lab and collaborators at the Salk Institute have discovered some of the specific signaling molecules involved in tumor progression in pancreatic cancer. These molecules, called eicosanoids, play a role in inflammation and are known to have a role in cancer. According to DelGiorno, that role had not been completely evaluated in pancreatic tumors—until now.
DelGiorno and her colleagues, including Vikas Gubbala, the paper's first author and lab technician at the Salk Institute, used advanced basic science technologies, including mass spectrometry—technology to measure the weight and charge of molecules—RNA sequencing and tissue study techniques called histopathology. The combination of these techniques helped them identify which eicosanoids are relevant to disease progression in pancreatic cancer and which cell types produce these signals. Collectively, these data provide a road map for what pathways to target and may help identify new diagnostic strategies.
In cancers with a low five-year survival rate like pancreatic cancer, discovering early signs of tumor formation and progression can be critical in developing new therapies to treat them.
Pancreatic cancer is the third leading cause of cancer deaths in the U.S. and is on its way to becoming the second, DelGiorno said. "This is largely due to how late we are currently able to diagnose pancreatic cancers, as well as the unique microenvironment with pancreatic tumors that lead to treatment resistance."
Immunotherapy is increasingly becoming a successful way to treat cancer. Researchers at Uppsala University have now developed armed CAR-T cells that reinforce the immune defense against cancer and that could increase the possibilities to successfully treat solid tumors. The study has been published in the journal Nature Biomedical Engineering.
The use of immunotherapy to treat cancer is increasing and genetically modified immune cells called CAR-T cells are efficacious for treating blood cancer. Unfortunately, their efficiency is impaired in solid tumors due to local immune suppression in the tumor.
To avoid this problem, the Uppsala researchers have armed CAR-T cells by introducing a gene that encodes the immune stimulatory protein NAP (neutrophil-activating protein) from the bacteria Helicobacter pylori. When NAP is released from the CAR-T cells this creates a proinflammatory environment which directly combats the immunosuppressive microenvironment in solid tumors and strengthens the function of the CAR-T cells.
CU Boulder researchers have discovered a new way to inhibit the most commonly mutated gene underlying human tumor growth, opening the door to new therapeutic strategies for cancer and a host of other diseases.
The discovery, published April 5 in the journal Cell Reports, marks an important step forward in the decades-long quest to target transcription factors (TFs), a notoriously hard-to-block class of proteins which, when mutated or dysregulated, can disrupt cell function and drive illness.
"This class of proteins represents one of the most high-impact therapeutic targets in biomedicine," said senior author and biochemistry Professor Dylan Taatjes. "We provide a completely new strategy for blocking transcription factor function that could have broad applications to many diseases, including and beyond cancer."
(EurekAlert) Milwaukee, April 8, 2022 – A novel therapy studied at the Medical College of Wisconsin (MCW) Cancer Center has led to a clinical trial for the treatment of glioblastoma, a rare and aggressive form of brain cancer, yet the most common primary brain tumor in adults.
Despite decades of research globally, only incremental gains have been made to extend or enhance quality of life for patients with glioblastoma. Treatment options are limited and typically include a combination of surgery, radiation therapy, and chemotherapy. Now, a new clinical study open at Froedtert & the Medical College of Wisconsin will evaluate an alternative treatment that is administered orally.
The treatment evolved from years of research led by Christopher Chitambar, MD, and his lab to study iron-dependent processes in cancer biology and the mechanisms by which gallium compounds target iron metabolism and block malignant cell growth. In preclinical studies, Drs. Chitambar and Kathleen Schmainda, PhD, discovered that when administered intravenously, gallium maltolate (GaM) significantly slowed the growth of glioblastoma in a rat brain tumor model. Additional studies showed that GaM, administered orally to glioblastoma-bearing rats, significantly reduced the size of their tumors and prolonged survival.
GaM, originally developed by Harvard and Stanford educated scientist Lawrence R. Bernstein, PhD, is an orally available form of the metal gallium, which, in the body, shares many chemical properties with the highly oxidized form of iron, Fe(III). Numerous studies examining the relationship between iron and cancer show that increased levels of iron in the body can be associated with increased cancer risk and severity, due to cancer cells’ dependence on iron to multiply and spread. Because of gallium’s similarity to Fe(III) (the form of iron cancer cells take up), cancer cells take up gallium instead of iron, preventing their multiplication, ultimately leading to their death.
“The discovery that GaM has anticancer activity against glioblastoma in pre-clinical studies is extremely exciting; it opens the door for developing it as a drug for treatment of glioblastoma in patients,” says Christopher Chitambar, MD, Emeritus Professor of Medicine and Biophysics, Division of Hematology and Oncology at MCW. “The anticancer mechanism of GaM applies to other solid tumors as well,” he adds.
(University of Ottawa via EurekAlert) A research team based at the University of Ottawa and The Ottawa Hospital has developed a virus that infects and kills cancer cells without harming normal cells, while also sending out signals to prepare nearby uninfected cancer cells for viral attack. Their new study, published in Nature Communications, shows that this novel strategy can shrink tumours and significantly prolong survival in several cancer models in mice.
The strategy relies on extracellular vesicles, tiny particles that pinch off from a cell and fuse with other cells. The research team created a virus that causes infected cells to produce extracellular vesicles filled with a specific RNA that blunts the antiviral defenses of nearby cancer cells. They found that this novel virus can work with other forms of immunotherapy, as well as with small-molecule drugs, to enhance cancer-killing even further.
“Cancer cells are constantly evolving new ways to evade our therapies, so we designed this therapy to target cancer on multiple fronts at the same time,” said senior author Dr. Carolina Ilkow, Assistant Professor in the Faculty of Medicine and Senior Scientist at The Ottawa Hospital. “We believe these observations are transformative for the fields of oncolytic viruses, miRNA therapeutics and exosome-based therapies.”
The researchers note that while many groups are investigating therapies based on RNA and extracellular vesicles, these therapies are much more difficult to manufacture and store than viral therapies. This new viral technology could have a broad impact, as it provides an easy and targeted way to “manufacture” and deliver RNA therapeutics and extracellular vesicles right inside the patient, rather than in a lab.
This research used a Maraba virus that has been tested in human clinical trials as a cancer therapy, but the strategy could be applied to other viruses as well. The researchers used several different models of pancreatic cancer (mouse and human) as well as models of ovarian, breast, kidney and skin cancer.
(Media College of Georgia via EurekAlert) AUGUSTA, Ga. (April 11, 2022) – Georgia counties with the highest mortality rates from four common cancers tended to be more rural, have higher poverty rates, have a higher percentage of Black residents and/or older individuals, according to researchers at the state’s public medical school and Georgia Cancer Center.
Georgia’s hotspots for death from breast, prostate, colorectal and lung cancer over a 20-year period from 1999 to 2019 were concentrated in the eastern Piedmont to the southern-most Coastal Plain regions, as well as the southwestern rural and northern-most rural areas, says Dr. Justin Xavier Moore, epidemiologist at the Medical College of Georgia and Georgia Cancer Center.
“We observed distinct geographic and racial/ethnic disparities in mortality from breast, colorectal, lung and prostate cancer,” Moore and his colleagues write about Georgia’s hotspots for some of the leading causes of cancer death.
“Now that we understand these are hotspot areas, we need to understand what is really driving that,” Moore says.
He is presenting the findings at the American Association for Cancer Research Annual Meeting in New Orleans April 8-13. Moore also is being honored at the meeting by the association with a Minority and Minority-Serving Institution Faculty Scholar in Cancer Research Award for his work.
