Breast cancer is the leading cause of cancer-associated death for women worldwide. While chemotherapy is the mainstream treatment for breast cancer, more than 50% of women undergoing chemotherapy will experience at least one chemotherapy-related adverse side effect. Sometimes, the side effects could be so severe that patients need to terminate treatment early or doctors have to reduce the chemo dosage, and this could worsen their disease. Prolonged exposure to high doses of chemotherapeutic agents could also result in resistance to chemotherapy.
A team of researchers from the National University of Singapore (NUS) is pioneering a novel magnetic therapy—delivered using the OncoFTX System—that serves as an effective companion therapy to chemotherapy to enhance treatment outcome for breast cancer.
Based on the findings of a new study led by the Translational Genomics Research Institute (TGen), part of City of Hope, a coast-to-coast clinical trial is planned that, if successful, could lead to FDA approval of the first new drug treatment in more than a decade for glioblastoma, the most common and aggressive type of brain cancer.
Using precision medicine to select only participants with a specific genomic "signature of vulnerability," researchers expect the new treatment could help up to a third of all glioblastoma patients. An estimated 18,000 Americans are expected to die this year from brain cancer, the nation's seventh leading cause of cancer death.
Results of a preclinical study published in Neuro-Oncology suggest that a drug combination of MLN4924, also known as Pevonedistat, when given in combination with a second drug called Etoposide, could help glioblastoma patients whose cancer cells have lost PTEN, a tumor-suppressor gene.
Genomic sequencing of patient-derived tissue samples showed those samples with a loss of PTEN also showed a spike in the expression of a gene called TOP2A, which research suggests resists the effectiveness of MLN4924. By using Etoposide to block TOP2A, researchers believe glioma cells will be weakened enough for MLN4924 to kill the cancer.
A protein called CDC7, long thought to play an essential role early in the cell division process, is in fact replaceable by another protein called CDK1, according to a study by investigators at Weill Cornell Medicine and the Dana Farber Cancer Institute. The finding represents a fundamental advance in cell biology and may lead to new cancer therapies, since cancers frequently alter the molecular machinery of cell division to sustain their rapid growth.
Starting screening before age 50 is found to significantly reduce the risk and incidence of colorectal cancer in women https://medicalxpress.com/news/2022-05- ... ectal.html
by Katie Marquedant, Massachusetts General Hospital
Screening for colorectal cancer (CRC) in women before the age of 50 can significantly reduce the risk of CRC compared to those who have no endoscopic screening or decide to initiate testing at age 50, according to a new study from Massachusetts General Hospital (MGH). These findings, published in JAMA Oncology, support recommendations from the American Cancer Society and the U.S. Preventive Services Task Force over the past four years to commence screening at age 45 to address the steady increase in cases of younger-onset CRC.
"While there's been an alarming increase in the incidence of colorectal cancer in recent decades in younger individuals, screening has largely been focused on people over 50," says Andrew Chan, MD, MPH, a gastroenterologist and epidemiologist at MGH, and senior author of the study. "Our work provides first-of-its-kind data to show that initiating screening at a younger age can reduce an individual's risk of colorectal cancer and the population's overall incidence of cancer, thus demonstrating the substantial impact of earlier screening on both individual and population-wide scales."
Overall evidence to date on whether eating dairy products affects the risk of cancer has been inconsistent. Studies on Western populations indicate that dairy products may be associated with a lower risk of colorectal cancer and a higher risk of prostate cancer, but have found no clear link for breast or other types of cancer. These results, however, may not be the same for non-Western populations, where amounts and types of dairy consumption and ability to metabolize dairy products differ greatly.
For instance, in China there is very little consumption of cheese and butter, and the consumption of milk and yogurt is also far lower than Western populations. In addition, most Chinese adults cannot properly metabolize dairy products due to lack of lactase, a key enzyme for breaking down the milk sugar lactose.
To establish whether dairy products affect the risk of cancer differently in Chinese people, researchers from Oxford Population Health, Peking University, and the Chinese Academy of Medical Sciences, Beijing, have today published the results of a new large-scale study in BMC Medicine. This collected data from over 510,000 participants in the China Kadoorie Biobank Study.
The participants (59% female, 41% male), who came from ten geographically diverse regions across China and joined the study between 2004 and 2008, had no previous history of cancer. When recruited, each participant (aged 30–79 years) completed a questionnaire about how frequently they consumed different food products, including dairy products. The researchers categorized the participants into three groups: regular dairy consumers (at least once a week), monthly dairy consumers, and people who never or rarely consumed dairy products (non-consumers).
Immunotherapy unleashes the power of the immune system to fight cancer. However, for some patients, immunotherapy doesn't work, and new research may help explain why. When immune cells called T lymphocytes infiltrate malignant tumors, the genetic program of those T cells and the developmental path they then follow, may affect their response to immunotherapy and predict overall patient survival, according to a new study by Weill Cornell Medicine investigators. The results overturn the prevailing model of immune responses in melanoma and present different therapeutic approaches.
In the study, published May 9 in Cancer Cell, the investigators analyzed thousands of human tumor samples, plus individual human T cells across many data sets and tumor types, and compared these to many models of T cell behavior in response to infections, cancer and vaccines, including human vaccines. They found that T cells either become stuck in an early activation state or develop into memory cells that are expanded by current immunotherapy approaches.
"The T cells don't behave in a singular manner, but we can understand their behavior and model it in a way that can predict patient outcomes and overall survival," said senior author Dr. Niroshana Anandasabapathy, associate professor of dermatology and of dermatology in microbiology and immunology at Weill Cornell Medicine, and a practicing dermatologist for melanoma patients at New York-Presbyterian/Weill Cornell Medical Center.
Research from the University of Michigan Rogel Cancer Center could provide a new approach to treating an aggressive form of breast cancer.
A study led by Duxin Sun, Ph.D., found that targeting the immune microenvironment in lymph nodes and tumors simultaneously led to long-term tumor remission in mice models of metastatic triple negative breast cancer. Further, using nanoparticles to deliver these immune-altering drugs increases treatment efficacy. These results appear in Science Translational Medicine.
Immunotherapy combined with chemotherapy has been long approved as standard treatment option for triple negative breast cancer but only shows a limited response in patients. Many believe that the tumor immunosuppressive microenvironment is one of the main contributing factors for the poor responses in those with TNBC.
Sun, Charles R. Walgreen Jr. Professor of Pharmacy and Professor of Pharmaceutical Sciences at the U-M College of Pharmacy, says that previously developed immunomodulators work well in animal models, but fail in clinical trials. He and his team wanted to come up with a better approach that would treat TNBC patients long-term that could withstand the rigor of clinical trials. To do this, they had to look beyond just the tumor microenvironment to the lymph nodes.
An article published in Scientific Reports describes a study demonstrating the effectiveness of a peptide developed by Brazilian scientists, called Rb4, in combating cancer progression in an animal model, especially malignant melanoma. The molecule holds promise for the treatment of drug-resistant tumors.
Preclinical in vitro and in vivo trials indicated that Rb4 triggers necrosis in murine melanoma cells, and inhibits the viability of human cancer cells. Tumor cells in the study lost the integrity of their plasma membranes, and mitochondria (energy-producing organelles) dilated even in the absence of chromatin condensation, a morphological hallmark of apoptosis. How this necrosis is triggered is still poorly understood, the researchers acknowledge.
In mice, the peptide reduced lung metastasis and slowed subcutaneous melanoma growth. The results suggest that Rb4 acts directly on tumors, inducing expression of two damage-associated molecular patterns (DAMPs), which trigger immunogenic melanoma cell death.
"We do basic science in a search for novel molecules. In this study Rb4, which is derived from proteolipid protein 2 [PLP2], displayed a preference for causing necrosis, a specific type of cell death, especially in melanoma, but how this necrosis occurs and develops isn't clear. The article discusses some aspects of the peptide's morphological composition and the final effects of contact with it," Fabrício Castro Machado, a co-author of the article, told Agência FAPESP.
A team led by Professor of Biology, Senior Vice Provost of Research at NYU Abu Dhabi, and UAE national Sehamuddin Galadari, has discovered a novel structural modification in AMP-activated protein kinase (AMPK) during anticancer therapy that could pave the way for the development of more effective cancer treatments.
AMPK normally works as the cellular energy sensor that is activated when there is a shortage of energy in the body. Once activated, AMPK kickstarts events in the cell that restore the energy balance. The major component of AMPK exists as two isoforms (functionally similar proteins)—AMPK-⍺1 and AMPK-⍺2.
In a paper appearing in Nature today, an international group of scientists report a new way to kill hard-to-treat cancers. These tumors resist current immunotherapies, including those using Nobel Prize-winning checkpoint-blocking antibodies.
The approach exploits Z-DNA. Rather than twisting to the right like B-DNA, Z-DNA has a left-handed twist. One role for Z-DNA is to regulate the immune response to viruses. The response involves AADR1 and ZBP1, two proteins that specifically recognize Z-DNA. They do so through a Zα domain that binds to the Z-DNA structure with high affinity.
The Zα domain was originally discovered by Dr. Alan Herbert of InsideOutBio, a communicating author on the paper. The ADAR1 Zα domain turns off the autoimmune response, while the other ZBP1 Zα turns on pathways that kill virally infected cells, as previously shown by Dr. Sid Balachandran, the other communicating author on the paper. The interactions between ADAR1 and ZBP1 determine whether a tumor cell lives or dies.
A research team at the School of Biological Sciences, the University of Hong Kong (HKU), has revealed novel cellular and molecular interactions between cancer cells and tumor-associated macrophages that promote peritoneal metastasis of ovarian cancer. These findings provide important insights into the therapeutic strategy of ovarian cancer and are now published in Advanced Science, an interdisciplinary open-access journal.
Ovarian cancer is the leading cause of deaths among all gynecological cancers. More than 70% of patients are diagnosed at an advanced stage with metastatic diseases. Peritoneal metastasis is very difficult to treat due to tumor heterogeneity and the dynamic interactions of cancer cells with the tumor microenvironment. The lack of suitable experimental models has been one significant obstacle to study the cellular and molecular mechanisms of this critical process, and the distinct interactions among different cancer cell subclones and tumor microenvironment are largely unknown using traditional bulk measurement.
Key findings: In metastatic ovarian cancer cells, Wnt/b-catenin signaling upregulates the expression of metadherin, which communicates with macrophages through CEACAM1, a carcinoembryonic antigen expressed by macrophages, suggesting that blockade of macrophage-tumor communications (by inhibiting either metadherin or CEACAM1) could greatly reduce peritoneal metastasis.
Michigan State researchers are revealing the molecular workings of how a certain form of metastatic breast cancer spreads to other parts of the body. In doing so, they're creating new opportunities to spot and contain what is called triple negative breast cancer.
"We focused on triple negative breast cancer, or TNBC, because it occurs proportionally more often in younger patients and has worse clinical outcomes," said Sophia Lunt, an associate professor in the College of Natural Science at MSU.
"The vast majority of TNBC-related deaths are due to metastasis, the spread of cancer cells from the primary tumor to other sites in the body," Lunt said. "Metastatic breast cancer is not curable, and available treatments aim to only slow disease progression."
Since joining MSU in 2015, Lunt's research has focused on understanding the role of metabolism—which nutrients and compounds cancer cells use and how—in metastasis. She and her team are now reporting results from their work on triple negative breast cancer, so named because its tumor cells test negative for three types of proteins used in diagnoses.
T cells, biology textbooks teach us, are the soldiers of the immune system, constantly on the ready to respond to a variety of threats, from viruses to tumors. However, without rest and maintenance T cells can die and leave their hosts more susceptible to pathogens, Yale scientists report May 27 in the journal Science.
"We may have to change how we teach T cell biology," said Lieping Chen, the United Technologies Corporation Professor in Cancer Research at Yale, professor of immunobiology, of dermatology, and of medicine and senior author of the study.
Until pathogens are detected, T cells remain in a quiescent state. However, the molecular mechanisms that keep T cells inactive were previously unknown.
In the new study, Yale researchers show that a protein known as CD8a—which is found in a subset of T cells called CD8 cells—is crucial to keeping the cells in this dormant state. When scientists deleted this protein in mice, the protective CD8 cells were unable to enter a quiescent state and died, leaving the host vulnerable to infections.
Researchers at The University of Texas MD Anderson Cancer Center have developed an ultrasound-guided cancer immunotherapy platform that generates systemic antitumor immunity and improves the therapeutic efficacy of immune checkpoint blockade. The findings from the preclinical study were published today in Nature Nanotechnology.
As the first-of-its-kind platform, the Microbubble-assisted UltraSound-guided Immunotherapy of Cancer (MUSIC) approach employs nanocomplexes combined with microbubbles to effectively deliver cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an immunotransmitter involved in anticancer immunity, into antigen-presenting cells (APCs). Inside the APCs, the microbubbles release cGAMP to activate the GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which stimulates type I interferon responses that are essential for priming tumor-specific T cells.
In the preclinical study, the MUSIC strategy demonstrated a complete tumor eradication rate of 60% when administered as monotherapy in breast cancer models. When combined with an anti-PD-1 antibody, MUSIC significantly improved antitumor responses with minimal toxicity effects, including enhanced primary tumor control and decreased systemic disease progression. In addition, the combination therapy demonstrated superior survival benefit, with a 76% increase in median survival compared to either therapy alone.
New Study Shows Racial Disparities in Guideline-Concordant Care for Early-Onset Colorectal Cancer Patients
May 31, 2022
Entire article less brief description of the American Cancer Society and disclaimer:
(EurekAlert) In a new large national study led by researchers at the American Cancer Society (ACS), Black patients diagnosed with early-onset colorectal cancer received worse and less timely care than their white counterparts. Differences in health insurance coverage type, a modifiable factor, according to the findings, were the largest identified contributor to the racial disparities. The study results will be presented at this year’s annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, June 3-7.
In the study, led by Dr. Leticia Nogueira, senior principal scientist, health services research at the American Cancer Society, more than 147,000 non-Hispanic Black and white individuals aged 20-49 years newly diagnosed with colorectal cancer during 2004-2019 were selected from the National Cancer Database. Patients who received all care recommended by the National Comprehensive Cancer Network (staging, surgery, lymph node evaluation, chemotherapy, and radiotherapy) for which they were eligible according to cancer subsite and clinical and pathological TNM stage were considered guideline-concordant. Demographic characteristics (age and sex), comorbidities, and health insurance coverage type were added sequentially to a series of multivariable models to estimate the contribution to racial disparities in receipt of guideline-concordant care. Racial disparities in time from diagnosis date (among rectal cancer patients eligible for neoadjuvant chemotherapy) and surgery date (among colon cancer patients eligible for adjuvant chemotherapy) to date of chemotherapy initiation was evaluated using restricted mean time to treatment.
Of the 84,728 colon and 62,483 rectal cancer patients included in the study, 20.8% and 14.5% were Black, respectively. Black patients were 18 and 36% less likely to receive guideline-concordant care than white patients diagnosed with colon and rectal cancer, respectively. Demographic characteristics and comorbidities combined explained less than 5% of the disparity, while health insurance coverage type explained 28.6% and 19.4% of the disparity among colon and rectal cancer patients, respectively. Restricted mean time to chemotherapy was statistically significantly longer among Black than white patients for colon (54.0 vs. 48.7 days) and rectal cancers (49.6 vs. 40.9 days), respectively.
Study authors stress improved access to care could help mitigate disparities in cancer outcomes.
Genetically engineered immune cells successfully target the specific cancer cells that may be responsible for relapse of acute myeloid leukemia (AML), a type of blood cancer, and proved effective in animal models of the disease, according to a preclinical study by investigators at Weill Cornell Medicine. The new cell therapy, now being tested in phase 1 clinical trials, may ultimately help patients with AML to remain cancer-free.
In the study, published April 28 in Nature Communications, the researchers used an approach in which immune cells known as T cells are directed to produce proteins called chimeric antigen receptors, or CARs, that enable the T cells to recognize specific markers on cancer cells. In this case, the CAR is a receptor that binds to the CD123 molecule on leukemia stem cells, enabling the T cells to seek out and attack the cancer cells.
"Leukemia stem cells are a subset of leukemic cells that are resistant to standard chemotherapy drugs and can cause disease relapse," said co–senior author Dr. Monica L. Guzman, associate professor of pharmacology in medicine in the Division of Hematology & Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. "CD123 is a marker found on leukemia stem cells, and my laboratory has been working on designing mouse models to test new CD123-targeted anti-leukemia therapies."
A combination of chemotherapy with an immunotherapy meant to unleash the anticancer capacity of the immune system was effective against one of the hardest targets in cancer care, pancreatic cancer, in a national, randomized clinical trial led by researchers at the Perelman School of Medicine at the University of Pennsylvania, and sponsored by the Parker Institute for Cancer Immunotherapy.
The results of the small but promising trial were announced today in a presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, and simultaneously published in Nature Medicine.
The researchers found that in 34 patients with advanced pancreatic cancer randomized to receive the immunotherapy nivolumab with two chemotherapy drugs, nab-paclitaxel and gemcitabine, had a one-year survival rate of 57.7 percent, significantly greater than the historical average of 35 percent with chemotherapy alone. The findings also included the identification of immune system biomarkers associated with better outcomes. A second treatment of the immunotherapy sotigalimab with chemotherapy also appeared more effective in a subgroup of patients, identified with a different set of biomarkers.
"This study suggests there is benefit of combining immunotherapy and chemotherapy in patients with advanced pancreatic cancer and there may be ways to fine tune treatment choices based on the 'immune health' of the patient," said Robert H. Vonderheide, MD, DPhil, the John H. Glick Abramson Cancer Center Professor and director of the Abramson Cancer Center at Penn. "We now hope to evaluate these potential biomarkers in further trials to see if they'll enable us reliably to identify patients who will respond best to this and other combination therapies. The most promising biomarkers were measured by a blood test of the immune system, not genetic sequencing, which opens the door for a new approach in precision oncology."
As people across the globe look forward to longer life expectancies, malignant cancers continue to pose threats to human health. The exploration and development of immunotherapy aims to seek new breakthroughs for the treatment of solid tumors.
The successful establishment of anti-tumor immunity requires the activation, expansion and differentiation of antigen-specific lymphocytes. This process largely depends on specific interactions between various T cells and antigen-presenting cells (APCs) in the body. However, existing tumor vaccines, such as neoantigen vaccines and various vector vaccines, all rely on random interactions with APCs in the body. Furthermore, inappropriate interactions may lead to the silencing of other immune responses.
Although immune checkpoint-based immunotherapy has been shown to have great potential, only a small proportion of patients fully respond to this therapy, and the relevant molecular mechanisms need to be further explored. This delivery method is however complex and inefficient.
In a breakthrough development, a team of scientists led by Narat Muzayyin Chair Professor Chen Xiaoyuan from the NUS Yong Loo Lin School of Medicine and Professor Liu Gang from Xiamen University has formulated a novel vaccine which showed high efficacy in the treatment of solid tumors, achieving complete clearance of solid tumors and inducing long-lasting immune memory. This prevents the relapse of tumor growth that the patient originally presented with and provides immunity against similar tumor types. This was proven through the application of this vaccine on melanoma tumor models. Their results are published in Nature Nanotechnology.
