Sarcoma tumors is a rare cancer that starts in our body’s connective tissues. These cancers spread quickly and less than 40% of people survive more than a year after it spreads. We need better treatments. One big issue is tumor hypoxia, or a lack of oxygen in the tumor. When tumors grow fast, they cannot get enough oxygen, which makes it hard for our bodies and treatments to fight off the cancer.
We have come up with a new method to get oxygen directly to the tumor using special materials called gas-entrapping materials (GeMs). These GeMs are made in a way similar to making whipped cream in a coffee shop. We plan to use GeMs to deliver oxygen to the tumor, which we believe could make treatments like immunotherapy work better and more safely.
Our research goal is to use a new series of GeMs to release oxygen into the tumor to help fight tumor hypoxia. Making GeMs is simple, cost-effective, and uses components considered safe. We think that using GeMs to increase oxygen could make immunotherapy more effective for spread-out sarcoma tumors.
We hope our research will show that these materials can be safely used with immunotherapy to help the body’s immune response fight the disease. This could mean a new way to get oxygen to tumors and could change how we treat sarcoma and other cancers that have spread to other parts of the body.
Anti-cancer monoclonal antibodies (mAbs) are a type of treatment for cancer that has helped many patients but they do not work for everyone. The overall goal of our research is to make mAbs better cancer treatments. MAbs stick to cancer cells and attract cells of the immune system known as Natural Killer cells (NK cells) that then kill the mAb-coated cancer cells. We have found that NK cells start to kill mAb-coated cancer cells, but stop killing cancer cells unless they get help from a different type of immune system cell known as T cells. This suggests one reason mAb might not work for some patients is a lack of help from T cells. We also found that a different type of antibody known as a bispecific antibody (bsAb) can increase the help T cells provide to NK cells. This suggests the combination of bsAb to mAb could be a better treatment for some cancers. In this project, we will conduct studies in both mouse models and in samples obtained from patients to evaluate the role of T cell help in anti-cancer mAb therapy and determine whether giving mAb and bsAb together is a better approach to cancer therapy. Our studies are focused on lymphoma, but the results could result in improved mAb therapy for a variety of cancers.
Supported by Bristol-Myers Squibb through the Robin Roberts Cancer Thrivership Fund
Cancer survivors often continue to havecertain side effects of anti-cancer drugs long after treatment has ended. Their hands and feet may feel numb, or they may feelunpleasant sensations in their hands and feet like burning. The simple touch of clothing or holding a cold can of soda may feel painful. Pin prick or paper cuts may hurt more than expected. These abnormal sensations are called chemotherapy-induced peripheral neuropathies (CIPN). They can seriously diminish the quality of life, and interfere with self-care and activities of daily living. Sixty-eight percent of patients report these abnormal sensations when asked 30 days after the end of anti-cancer treatment.Although the abnormal feelings may decrease over time, they can persist for months to years in as many as 30% of cancer survivors. Advances in diagnosis and treatment of cancer have increased the number of survivors to nearly 14.5 million. Of these, up to 4.5 million may continue to suffer CIPN long after their treatment has ended. There are no effective drugs for these survivors. We recently discovered thatNIAGEN®, a type of vitamin B3 that increases levels of NAD+, can prevent abnormal sensations in a rat model of CIPN.Importantly, it can also reverse CIPN that persists after the last dose of paclitaxel. The goal of this study is to translate these laboratory findings to the clinic and the patient. Here, we will determine whether daily treatment with NIAGEN can relieveresidual persistent CIPN in cancer survivors.
Obesity, defined by body-mass index over 30.0, influences more than 30% of American adults and is associated with increased incidence and/or bad prognosis of various cancers including esophagus, pancreas, colon and rectum, breast, and endometrium etc. Obesity contributes directly to the 34,000 new cancer cases in men (4% of all cancer) and 50,500 in women (7% of all cancer) in 2007, based on the NCI Surveillance, Epidemiology, and End Results (SEER) data. In addition, obesity increases the risk for many different types of cancer including breast cancer and decreases patient survival and is associated with bad outcome. Obesity always correlates with increased basal level inflammation. It is unknown, however, if obesity-associated inflammation promotes cancer progression and what is the molecular sensor for obese tumor microenvironment. Here we found that sterile inflammation–a type of inflammation without clear infections and activated by danger signals released by tissue damage–in the obese tumor microenvironment, led to Nlrc4-inflammasome activation. We found that interleukin-1beta is the major downstream mediator for Nlrc4-inflammasome activation that provides a pro-inflammatory signal to be required for tumor growth in obese mice, but not in normal-weight ones, by promoting angiogenesis in obese tumors. Our goals are to understand how obesity contributes to cancer progression, and to develop treatments to obese cancer patients.
The proposed study has ground-breaking impacts on basic cancer biology and cancer therapy to obese cancer patients. For cancer biology, we identified the molecular sensor in obese tumor microenvironment and aim to detect ‘danger signal’ from obese tumors, which, in turn, promotes cancer progression via activation of interleukin-1beta. For cancer therapy, given that ~30% Americans are obese and many cancer types are influenced by obesity, our study will have big impact on cancer patients. Anakinra is a known decoy receptor to inhibit interleukin-1 receptor-mediated signaling and has been improved drug to treat rheumatic arthritis. Caspase-1 (the major enzyme for inflammasome-mediated interleukin-1beta activation) inhibitors have been in several clinical trials. In addition, we found that metformin reduces obesity-associated tumor growth. These drugs can be easily and quickly adapted for treating obese cancer patients, together with current standard care for cancer patients.
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