Funded with support from Hockey Fights Cancer powered by the V Foundation
Cervical cancer is highly preventable. However, it remains a health burden and is the fourth most common cancer in females around the world. Cervical cancer is caused by “high-risk” types of the human papillomavirus (HPV). Screening for cervical cancer using HPV is much more effective than the Pap test. However, HPV screening alone cannot determine if an HPV infection will resolve, or if it will progress to cervical cancer. We need to find better ways to identify the people with HPV who have the highest risk of cancer.
The microbiome of the vagina may play an important role in progression to cancer. Understanding more about the vaginal microbiome in those with high-risk HPV could help us determine when an HPV infection may resolve or when it may progress. This knowledge could lead to earlier and better treatment and prevent cervical cancer from developing.
This research will be done in British Columbia, Canada. We will determine the microbiome characteristics of an existing set of cervical samples. We will then link these characteristics to over 10 years of cervical cancer screening results. We will explore if certain microbiome characteristics can determine whether HPV progresses to cervical pre-cancer or if HPV will clear. These findings can lead to important advancements in HPV screening for cervical cancer. This study has strong potential to impact global cervical cancer prevention and treatment standards. The findings are especially important as screening programs around the world shift to HPV-based cervical cancer screening.
This research aims to improve cancer treatment, specifically immunotherapy. My lab will identify factors that determine patients’ immunotherapy responses. We already know that microbes in our gut impact cancer treatment. For example, research shows that a fecal microbiota transplant can overcome immunotherapy resistance. At first, our goal was to identify which microbes impact immune responses. However, a difficulty for this research was that the regions we live in change which types of microbes are in our gut. This is a problem because it makes it hard to validate findings between regions. Our work revealed that it is not the species of microbe that impacts immunotherapy responses, as we first thought. Instead, it is the types of proteins produced by these microbes that matter. Different species of bacteria can make similar proteins, and it is these proteins that drive immune responses. We developed a new strategy to identify the proteins that bacteria are producing in the gut. Our approach reveals a relationship between proteins and treatment response. We verified this relationship in melanoma patients from different regions. For our next steps, we propose identifying non-invasive immunotherapy biomarkers. We will do this with the fecal microbiome. We expect that our research will improve clinical decisions and treatment outcomes.
Pancreatic cancer is one of the deadliest cancers because it is very difficult to treat. There are only a few treatment options available, and they do not work very well for most patients. We propose to find new therapies by studying how certain molecules, called RNA-binding proteins (RBPs), contribute to pancreatic cancer growth. RBPs are important because they control how genes are translated into proteins and ensure that the right genes are expressed at the right time and in the right amounts. When they are not working properly, RBPs can contribute to cancer development. For example, how much of an RBP is made can be affected by certain changes in the cancer cells, like how genes are turned on and off. Additionally, how an RBP works can be affected by cancer-specific modifications to its protein structure. Our research will focus on understanding what goes wrong with RBPs in cancer and how we can fix it. We will determine which RBPs and which cancer-specific modifications of RBPs are important for tumor growth and drug resistance. This will help us find answers that could lead to new therapies for pancreatic cancer patients.
African Americans have the highest percentage of new cancer cases in the U.S. but are less likely to be in research. People ages 13-39 partake in research less than any other age group. Hispanic patients also participate less if they do not speak the language or their culture is different, so they need different care. Patients from rural areas have a hard time getting to a cancer treatment center or need help figuring out the system once they are there. People without health insurance or poor insurance plans have access to care and research issues. AHWFBCCC wants to make sure everyone has access to the best cancer care possible. The best care possible may mean a patient joins a clinical trial. It is important to make sure all people are spoken for in studies that look at new treatments or supports for cancer patients. To meet that goal, we started a population health navigator program- people who are from the community who can help people learn about cancer, how to prevent it, what screening is needed and what treatments are available. If someone is diagnosed with cancer, the navigator will help to remove barriers to care and will talk with them about research as part of their care.
Funded with support from the Michael Toshio Cure for Cancer Foundation
When a patient is diagnosed with cancer, they start treatment hoping to get rid of the unhealthy cells. But some cancers, including a common and aggressive type called squamous cell carcinoma, have an unsettling ability to resist treatment. When cancer cells escape therapy, patients may find that the tumor comes back after initially going away and that it starts to spread. Drug resistance is the main reason that cancers have been so difficult to eliminate. We know that genetic changes in healthy cells can cause cancer to form, but these don’t tell us why some cancer patients don’t respond well to treatment. My lab is developing new ways to observe how the surrounding healthy tumor environment is helping cancer cells resist therapy. We found that drug-resistant tumor cells rely on their connections with lymphatic vessels, typically considered as the waste drains of the body. Using a model of skin cancer, we are proposing a new tool to track cancer cells in their natural habitat to find how lymphatic vessels shield and protect the cancer cells. By targeting the supportive lymphatic network, we hope to prevent cancer cells from surviving therapy. We believe that our findings will lead to new ways to treat cancers and eliminating cancer relapse as a treatment fallout.
Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive type of malignant B-cell tumor. Despite progress in lymphoma treatment, up to 40% of patients will ultimately succumb to their disease. Chimeric antigen receptor (CAR) T-cells (CAR-T) are immune cells from patients where a patient’s own white blood cells are isolated and engineered to target and kill tumor cells. CAR-T cell therapies demonstrated an entirely new paradigm for cancer therapy and produced unprecedented initial responses in patients of relapsed or refractory DLBCL. However, our group and others recently observed that over half of patients on CAR-T therapy eventually had disease relapse and fatal progression due to development of resistance. Thus, there is an urgent need to improve the efficacy of response and delay or prevent CAR-T therapy resistance. To tackle this major obstacle, my group has developed sophisticated models and expertise to develop a novel strategy to target the tumor in a more precise, personalized manner to overcome chemo-, targeted- and CAR-T therapy resistance. Ultimately, we will rationally design and test the improved and safe combinations of CART with the newly discovered inhibitor for DLBCL therapy. The outcomes of this study have broad applicability 1) improve the current standard of care by overcoming refractory and relapsed DLBCL current therapy resistance, 2) enhance the CAR-T therapy efficacy, and 3), we anticipate, can be readily translated to improve quality of life and/or length of life and has immediate impact on DLBCL patient care.
The low number of minority populations in clinical trials leads to higher mortality in these groups. It is important to address these inequities in order to address these cancer disparities. By developing a program that addresses the needs of patients, clinics, institution and communities, we hope to support minority patients seeking care at DCI to lower the barriers to accessing life-saving cancer clinical trials.
North Carolina (NC) has the largest American Indian (AI) population east of the Mississippi River. Yet, we do not know much about the health and health care of AIs in NC. We do know cancer is their number one cause of death. We need to better understand cancer and cancer-related needs in this group to reduce the burden of cancer. Three NC cancer centers joined together in 2021 to learn more about how to help AIs with cancer. We will study how cancer of the liver and stomach affects American Indians in NC. And we want to find and create resources for our AI community. First, we will use the NC Cancer Registry and health insurance files to learn more about how and where AIs in NC get cancer care and any potential disparities. We will then have a community event to test for and treat the top cause of stomach cancer. Lastly, we will educate about liver and stomach cancer to help prevent them. This work will help AIs in NC by showing what the greatest needs are and the opportunities for better care. The long-term goal is to improve cancer outcomes in all AIs.
Head and neck cancer is deadly because there are no effective drugs. Cisplatin is a commonly used drug for cancer treatment. However, patients with head and neck cancer usually develop resistance to this drug, which eventually leads to death. Although cisplatin can effectively kill most cancer cells, it is less effective in killing a specific type of cancer cells called cancer stem cells, which are responsible for the regrowth of the cancer after cancer therapy. Accordingly, inventing a new drug that can effectively kill cancer stem cells will improve patient survival. However, no drugs are available for killing cancer stem cells. Identifying key players maintaining cancer stem cell growth will help develop more effective drugs. Recently, we found a protein named FOSL1 is required to maintain cancer stem cell growth in head and neck cancer. However, the reason why FOSL1 keeps cancer stem cells growing is not fully understood. We also found a drug that can block FOSL1 function to prevent cancer stem cell growth. However, the efficiency is low. To increase the treatment effect, we developed a more potent compound based on this drug that can more effectively kill cancer stem cells 100 times in head and neck cancer. Our goals are: 1) using this compound to explore why FOSL1 can maintain cancer stem cell growth; 2) determine whether this compound can overwhelm cisplatin resistance using animal models. The knowledge obtained in this study will lead to developing more effective drugs to improve head and neck cancer patient survival.
Clinical trials are used to test new cancer treatments that may improve patient survival. Black or African American (AA) patients are less likely to be treated in a clinical trial than White patients. One way to try to reduce this inequality is to use specially trained staff to help people with cancer better understand clinical trials. These staff are called patient navigators. In this project, we will use patient navigators to teach and support patients with cancer and help them overcome barriers to joining clinical trials and gaining access to new treatments. These navigators will focus on making sure all Black/AA patients with endometrial cancer or prostate cancer who receive care at the Cancer Center are considered for cancer clinical trials. In addition to teaching patients about clinical trials, the navigators will also help them better understand the hospital system and make and keep appointments. They will assist patients who live far from the cancer center with travel and with finding a place to stay when they come for appointments. They can connect patients to finance counselors, social workers, and other helpful community services. To understand if the project is a success, we will compare the total number of patients, by race, treated on cancer clinical trials before and after the project. We will also study why patients chose not to be on clinical trials even when they are eligible. This information will help us design new projects in the future.
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