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."
