Facilitate the transition of projects from the laboratory to the clinic. Translational researchers seek to apply basic knowledge of cancer and bring the benefits of the new basic-level understandings to patients more quickly and efficiently. These grants are $600,000, three-year commitments
Funded with support from Dave and Rhea Benson in honor of Angela Sbarra
The rates of rectal cancer are increasing in young adults. Treatment for rectal cancer includes chemotherapy, radiation, and surgery. These therapies can have a negative effect on the quality of life of survivors. Radiation can cause infertility and problems with bowel and bladder function, as well as sexual health. Up to one third of the patients need a permanent colostomy so they do not have normal bowel function. Due to these issues, there has been an interest in finding ways to improve treatment for rectal cancer so that radiation and/or surgery may not be necessary. One way we are trying to improve treatment of cancer, including rectal cancer, is with immunotherapy. Immunotherapy empowers the patient’s own immune system to fight cancer. When this happens, it is very effective. Funding from the V Foundation will support a clinical trial that will treat rectal cancer that is mismatch repair proficient with immunotherapy first. The project team believes that improved immunotherapies like Botensilimab (anti CTLA4) and Basltilimab (PD-1), and earlier treatment before the tumor has spread, will lead to responses. This research has the potential to change the treatment paradigm of all early-stage rectal cancers and omit radiation and surgery in those patients whose cancers disappear with immunotherapy and chemotherapy alone. This will be an important finding for patients’ quality of life. It will also teach us how to make the immune system work against cancers where it has not worked in the past.
In recent years, colorectal cancer (CRC) has become the third most common and second most deadly cancer in the US. CRC is the leading cause of cancer death among Americans under 50 years old, but experts do not know why rates are increasing among young people. Moreover, we do not have a good way of detecting people who are at higher risk of CRC. These people should receive early monitoring and undergo extra measures to prevent CRC. How can we identify these at-risk individuals? We propose that certain bacteria cause the production of an enzyme (DUOX2) in the gut. High levels of this enzyme are found in people with gut inflammation and people with CRC. In the proposed research, we plan to test whether patients with different types of CRC have different levels of DUOX2. We expect that some CRC types will have higher levels than others. Next, we will try to identify the bacteria that lead to high DOUX2 levels. Discovering these bacteria may help to identify people at higher risk of CRC (people with higher amounts of these bacteria) and suggest new cancer treatments (ones targeting these bacteria). Finally, we will test whether drugs that are already approved for use in humans, along with other products of bacteria, can reduce levels of DUOX2 in the gut. Identifying these drugs may improve prevention and treatment for CRC.
Surgery is the main treatment option for patients with rectal cancer. During surgery, the surgeon’s main goal is to completely remove cancer tissue without leaving cancer behind. However, not all diseased tissue can be seen with the surgeon’s eye, especially after radiation when tumor and scar look similar. Because of that, it is hard for a surgeon to be certain that all cancer tissue has been removed on the anal side to help preserve the anus and avoid a permanent bag. The same problem happens for adjacent organs such as the pelvic nerves, pelvic sidewall, vagina or prostate that may appear to be affected. Consequently, 4-20% of patients have recurrence while 20-50% have postoperative complications. Currently, there are no technologies that can help surgeons identify cancer tissues within the rectum and nearby organs in vivo during surgery. Surgeons are thus faced with the difficult decision to excise questionable tissue that could be affected by cancer at the devastating expense of compromising critical tissue structures and quality of life. In our study, we will evaluate the MasSpec (MS) Pen technology for tissue identification in rectal cancer surgery. The MSPen provides the transformative capability of detecting molecules diagnostic of cancer in tissues in vivo, without tissue damage. We will refine the MSPen for rectal surgery and evaluate its performance in identifying rectal cancer and normal tissues. The MSPen has the potential to help surgeons achieve complete cancer removal and preserve normal tissues, thus improving treatment, outcomes, and quality-of-life for patients.
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.
Funded by Hockey Fights Cancer™ Powered by the V Foundation
Meningiomas are the most common intracranial tumor in adults. While most meningiomas can be successfully treated with surgery, there are a significant proportion of cases that require the addition of radiation therapy to delay tumor recurrence. However, our current methods of selecting which patients should be escalated for radiation after surgery remain relatively imprecise, especially for intermediate-grade meningiomas that can behave in a highly variable manner. Molecular profiling, specifically DNA methylation of meningiomas has proven to be an effective and efficient method of providing additional information on these tumors that can be used to better predict whether they will or will not recur after surgery. However, whether a similar set of molecular signatures exist to predict whether a meningioma of any given patient will respond to radiotherapy after surgery remain to be determined. This V Foundation grant will enable us to 1) develop a clinically important predictor using specific molecular signatures of any given patient’s meningioma to tell us whether their tumor will respond to radiation, 2) test this predictor through a novel, real-time, molecular-pathology informed clinical trial, and 3) determine if the same signatures that can prediction response to radiotherapy in the tumor tissue can be used to non-invasively provide the same information through a simple blood test. Results from this study have the potential to dramatically improve the way we treat patients with meningiomas and will represent a significant shift forward in the field of neuro-oncology.
Funded by the Dick Vitale Pediatric Cancer Research Fund and the StacheStrong Foundation
Clinical outcomes in children diagnosed with high grade glioma and diffuse intrinsic pontine glioma remain very poor. Even with surgical resection, chemotherapy and radiation, most of the tumors eventually relapse. This is primarily because some cancer cells develop resistant to the therapies that doctors prescribe. For the past 50 years, the identities of these therapy-resistant cancer cells remain unknown. Difficulties of obtaining relapsed tumor tissues and limited availability of animal models are the major reasons why we still don’t have new treatment. With the strong support of patients and families, we have developed a panel of animal models by directly implanting brain tumor cells into the brains of immunodeficient mice. We can now use these models to mimic what happens in children but treating the animals with the similar drugs/radiations. These models are very helpful. Indeed, our preliminary study in a small number of models have identified a set of cells expression CD57 as candidate root cells as they were found before drug treatment, remain present after very extensive clinical treatment, and can even survive the most harmful environment with no oxygen and no nutrient. This exciting finding has promoted us to perform a detailed analysis using more animal models to confirm the extraordinary capacity of the CD57+ cells in resisting therapy induced cell king, to understand how they can survive current treatment, and to find new drugs and strategies to selectively kill these seed cells. Our ultimate goal is to find new cure for children with highly malignant gliomas.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Children with muscle cancer commonly develop resistance to therapy. This is a major problem and most kids will die from resistant disease. Our group has developed a new combination of drugs to kill muscle cancers and is now being tested in kids and young adults. Yet, drug resistance to this same combination has been reported in other cancers and may develop in our patients. Our work will uncover how resistance develops and identify a new drug that can restore sensitivity to chemotherapy. This work is important because the new drugs we identify could be used to treat kids in the future.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Acute Lymphoblastic Leukemia (ALL) is a common cancer in kids. There are two types, B-ALL and T-ALL, depending on the type of white blood cells affected. Most kids get better with current treatments, but sometimes the cancer comes back and we can’t help them anymore. That’s why we need new treatments for T-ALL.
We know that certain drugs used in the hospital affect how leukemia metabolism works. So, we wondered if changing the diet could also help. In our lab, we tried different diets on mice with leukemia. Surprisingly, we found that removing just one component of the food (an amino acid), made a big difference. Leukemic mice eating food without this amino acid lived much longer. Now we want to understand why this dietary approach helps and if we can use it in combination with other treatments. We will study mice with leukemia and samples from real patients to see how this amino acid affects cancer. We also want to find out if combining this diet with current treatments works even better.
If our research is successful, we can try it on real patients. We want to see if reducing this amino acid in the diet can make treatments safer and help more kids survive, especially those whose cancer has come back. This research is important because it could give us new ways to treat leukemia and help more kids get better. It might even help with other types of cancer too.
Funded by the Constellation Brands Gold Network Distributors in honor of the Dick Vitale Pediatric Cancer Research Fund
Ewing sarcoma is a cancer that is most often diagnosed in teenage children and young adults. There is a need for new therapies for this disease. The goal of our work is to develop new therapies for Ewing sarcoma focused on a drug target called EWS-FLI1. Multiple studies have shown that EWS-FLI1 is a promising drug target for this disease. In a clinical trial called SARC037, we are currently testing a combination therapy that we have shown targets EWS-FLI1. The goal of the current study is to try to understand why some patients in this trial respond to the therapy and others do not. To accomplish this, we will study ways that EWS-FLI1 resists targeting. We will identify molecular differences in tissue collected from patients who had an excellent response to the therapy compared to those who did not respond. In addition, we will test these differences in the laboratory to see how they impact sensitivity to the therapy used in SARC037. The results will guide future clinical studies that seek to target EWS-FLI1. In addition, they will provide insight into how EWS-FLI1 contributes to drug resistance to more traditional chemotherapy.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Brain tumors are the leading cause of cancer-related death in children. While recent advances in neuro-oncology have helped us understand the biology of what is causing brain tumors to develop and grow, many children with brain tumors will still have a dismal prognosis. These tumors can be refractory to upfront treatment, such as radiation or chemotherapy, and there is need for better options. CAR T-cell therapy is a new type of treatment that uses the patient’s own immune cells and modifies them in the lab to recognize and kill cancer cells. CAR T-cell therapies are highly specific to the cancer cells. In our clinical study, we are evaluating the safety and anti-cancer activity of CAR T cells for pediatric patients with brain tumors.
