One challenge of lung cancer treatment is that cancer cells thrive in a tumor ecosystem (or habitat) that protects them. This tumor ecosystem consists of immune cells, blood cells, connective tissue that allow lung tumors to grow and spread to organs (brain, bones, liver, lungs). We recently discovered that PD1, AXL and STAT3 signals in lung cancer serves as “on switches” that drive lung cancer growth, treatment resistance and spread to organs. More importantly, these cancer signals allow cancer cells to communicate with nearby cells for protection. We found that blocking PD1, AXL and JAK signaling can block communication between tumor and non‐cancer cells in tumorecosystem. Our research team would like to perform mouse experiments and clinical trial using drug combinations that turn off these signals and disable the tumor within its habitat, thereby preventing tumor growth and spread. This therapy could help improve survival for our patients with lung cancer.
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.
Funded by Kay Yow Cancer Fund 2023 Final Four Research Award
One of the greatest challenges in cancer treatment is that response to standard treatment is frequently incomplete and causes many side effects. Current treatments are often ineffective because they function as a “one-size-fits-all” approach to a very personal disease. This lack of success is magnified in triple negative breast cancer (TNBC), which differs greatly between each individual. We have recently discovered a protein that is not expressed anywhere in females, except in TNBC tumors, where it is required for tumor growth. This protein is normally only found in male testes. Thus, this protein is a perfect target to inhibit tumor growth without impacting normal tissues. Here we will study the function of ZNF165 and determine how it promotes growth of tumors. Ultimately, this work could lead to a tailored approach for treating TNBC without harming the patient.
New cancer drugs are needed to improve quality of care, deliver cures, extend life and prevent relapse. We need to hunt in new places or in places that are not yet fully explored to come up with ideas for better drugs. We have focused on a previously overlooked area that is prime for exploitation, namely how DNA is packaged into cancer cells. DNA is the instruction manual of the cell and must be copied forward when cancer cells divide, a process called DNA replication. However, because DNA is so long it must be packaged correctly into the cell nucleus after it is copied. The cell makes a large number of DNA-packing proteins called histones to accomplish this task. We aim to find ways to attack a cancer cell’s ability to make histone proteins as a new cancer treatment strategy. We expect this be safer (less toxic) than targeting DNA replication itself, and hope to find ways to target it specifically to cancer cells. To do this, we are focused on the details of the DNA packing problem, by digging into the cellular components that control this process and asking molecular questions using the latest technologies. We want to understand how this process works better and how it goes awry in cancer cells so that we can exploit our findings for new drugs.
Liver cancer is among the top four causes of cancer death. Historically, liver cancer is driven by HCV. Now, liver cancer is the fastest-growing cause of cancer death in the United States. This is due to the increase of nonalcoholic fatty liver disease (NAFLD), affecting around 25% of the global population. Emerging evidence defines over-nutrition environment and circadian misalignment as risk factors for NAFLD and liver cancer. So far, there is no FDA-approved drug to target the progression of NAFLD to liver cancer. Therapeutic approaches for liver cancer are also limited. Therefore, it is important to understand the mechanisms behind NAFLD-related liver cancer and identify new therapeutic targets.
We reported that a lipid-lowering drug decreased liver fat more when given in the afternoon than when given in the morning. This work is an example of chrono-pharmacology, where giving drugs at specific times of the day can maximize efficacy. My recent work revealed eating time as a key pacemaker for rhythmic metabolic processes in the liver. We can find a potential preventive approach for metabolic disorders and cancer patients by exploring this relationship between the internal clock and eating time. Chrono-nutrition is adjusting diet schedules to maximize results for treatment. The future project will identify how circadian rhythm affects liver cancer cells. These studies aim to find new targets of circadian physiology and reveal insights into liver cancer prevention and treatment.
The Epidermal Growth Factor Receptor (EGFR) gene mutations can be detected in about 15% of patients with lung cancers. In female lung cancer patients who have never smoked cigarettes, as many as 50% of patients have this EGFR mutation. These mutations in the EGFR gene can be different from patient to patient, but all lead to the generation of an active protein that drives cells to survive, proliferate, and become cancerous. Currently, we have efficacious drugs for some of the EGFR mutations, but many other mutations do not have an approved drug. To address this unmet need, I am leading a clinical and translational research program including multiple clinical trials aiming to bring new approvals to treat those atypical EGFR mutations lung cancers. We will collect clinical information and bio-samples (both blood and tissue) to understand why some tumors respond to a certain drug, whereas other tumors not, to characterize the landscape of resistance mechanisms for each group of EGFR mutations. We will test a number of novel drug-drug combinations to overcome resistance and provide more potential options for EGFR mutation lung cancer patients. In this program, we will take a team approach to engage investigators with different expertise, use leading-edge technologies, including computational biochemical approaches and single-cell transcriptomics analysis, and ultimately nominate future therapeutic options for patients.
The study will detect cancer of the prostate in African-American men. African American men develop prostate cancer at a young age. The cancer spreads rapidly making it difficult to treat. Our method will detect substances produced by prostate cancer. The test will examine blood collected from men who have concerns with their prostate. The study will develop the test and make it available in the clinic. The test will help African American men in the community who do not have access to medical care. Early finding of prostate cancer will provide enough time for cure and will help reduce cancer related suffering and death.
Renal medullary carcinoma (RMC) is a rare but deadly kidney cancer that mainly occurs in young individuals of African descent that carry a blood disorder called sickle cell trait. Most people carrying the sickle cell trait never develop any symptoms. Many do not even know that they have it. Approximately 1 in 14 African Americans have the sickle cell trait and are at risk for developing RMC at an average age of 28 years old. RMC is also an under-recognized global health challenge because the sickle cell trait is found in ~300 million individuals around the world, mainly in Africa. Almost every patient with RMC is diagnosed late, when the cancer has already spread to other organs. Less than 5% of these patients survive beyond 3 years. Furthermore, many patients with RMC are initially misdiagnosed and lose precious time while being treated with the wrong therapies. The chances of a cure considerably increase when RMC is diagnosed and treated early. With the help of our patient advocates, we have established the largest collection of blood and tissue samples from patients with RMC worldwide. Using these samples, we have found evidence that patients with RMC have antibodies against unique proteins found only in cancer. We have developed a novel technology that allows the detection of more than 400,000 of these antibodies using only a drop of blood, quickly (within 3 days) and affordably. Our proposal aims to investigate and develop this new approach for the early diagnosis of RMC.
Funded by the Dick Vitale Pediatric Cancer Research Fund in memory of Colby Young
Children with changes in a pair of related genes (named DROSHA and DICER1) can get cancer in their lungs, muscles, kidneys, brains, and other organs. This is because DICER1 and DROSHA normally turn off pro-growth signals. When these pro-growth signals cannot be turned off, cancer can arise. We do not know which pro-growth signals are most important. Our lab found that one of these pro-growth signals, named Igf2, may be one of the most important. We came across this idea through studying mice that develop brain cancer due to Drosha changes. This project will study how important Igf2 is. It will also examine exactly how Igf2 gets turned on. Lastly, it will test whether a drug that targets Igf2 will be effective in these cancers.
Lung cancer is a deadly disease. One common cancer treatment called immunotherapy boosts the body’s natural defenses to fight the tumor. However, while some lung cancer patients respond well to immunotherapy treatments, other patients do not respond to the therapy. This suggests that we need to find new ways to improve these treatments. Our research supported by the V Foundation aims to improve the body’s ability to fight lung cancer. We will study mechanisms to boost the effects of immunotherapy and we will test these new approaches using cancer models. This work has the potential to improve immunotherapy and expand the use of these treatments for larger numbers of lung cancer patients.
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