Cowden Syndrome

Researchers are investigating targeted drug therapies for patients with vascular malformations that are resistant to standard treatments or for whom standard treatments are unsuitable. These vascular malformations are classified as either slow-flow or fast-flow types, driven by genetic changes in two specific signalling pathways. This phase II open-label trial aims to evaluate the effects of 48 weeks of treatment using either alpelisib for slow-flow vascular malformations with PI3K pathway mutations or mirdametinib for fast-flow vascular malformations with MAPK pathway mutations. Participants are divided into two treatment groups based on their vascular malformation type and genetic mutation. Those with slow-flow malformations and PI3K pathway mutations will receive alpelisib, an oral PI3-kinase inhibitor, for 48 weeks followed by a 24-week follow-up. Those with fast-flow malformations and MAPK pathway mutations will receive mirdametinib, an investigational oral MEK inhibitor, also for 48 weeks followed by 24 weeks of follow-up. Both treatments are given as monotherapy and involve genetic testing before enrollment to confirm mutations. Throughout the study, participants will undergo various assessments including symptom evaluations using the Vascular Malformation Patient Specific Outcome Measure (VM-PSOM) and OVAMA questionnaires, MRI scans to measure lesion size, and monitoring for adverse events. The primary outcome is the improvement in the most significant symptom after 48 weeks of treatment. Follow-up visits continue for 24 weeks after treatment ends to monitor ongoing effects and safety. The total participation duration for each patient is approximately 72 weeks.

RASopathies are genetic conditions that affect children's development, causing physical, cognitive, and behavioral challenges. This research aims to find out if Acceptance and Commitment Therapy (ACT), a technique that helps people accept difficult thoughts and feelings, can help caregivers of children with RASopathies manage parenting stress. The study includes an initial pilot phase followed by a randomized trial to compare immediate versus delayed intervention effects. The study involves an 8-week ACT intervention delivered remotely through a mobile app called MetricWire. Participants watch weekly videos lasting 9 to 17 minutes and engage in coaching sessions via video chat—one 75-minute session in week 1 and shorter 20- to 30-minute sessions in weeks 3 and 6. The trial has two phases: a pilot study where all participants receive the intervention immediately, and a randomized controlled trial where participants either start the intervention right away or after approximately 2 months on a waitlist. Caregivers aged 18 or older who care for a child under 18 with a RASopathy and live with the child at least half the time are eligible. They will complete brief daily surveys five days a week and longer questionnaires before and after the intervention, as well as three months later. These assessments measure parenting stress, mindfulness, self-compassion, and related factors. The study monitors feasibility, acceptability, and changes in stress levels over time using electronic assessments and questionnaires.

Researchers are evaluating new approaches to cancer genetic counseling to improve patient engagement with genetics teams. This study includes two trials: the EfFORT Trial focuses on cascade genetic testing, where healthcare providers reach out directly to family members at risk to recommend testing, comparing it to the usual method where patients inform their relatives. The STRIVE Trial studies an online portal intervention to help patients with uncertain genetic test results and their primary care providers stay updated on new information about those results. The EfFORT Trial compares a control group where patients share a family letter with relatives against an intervention group where providers contact relatives directly, offering telegenetics counseling and at-home saliva testing. The STRIVE Trial compares standard care with a digital portal called MyGene Portal, which offers ongoing access to educational materials, communication tools, medical history updates, notifications about result reclassification, and reminders for follow-up visits. Both trials include standard post-test genetic counseling and follow-up recommendations. Participants will be involved through genetic counseling sessions, use of the online portal, and study surveys. Assessments include measuring how often genetic testing occurs in relatives and participant-perceived quality of care over 12 months. Researchers monitor engagement with the interventions, update family medical histories, and provide support for uncertain genetic results. The study is randomized and open-label, with participants actively involved in education, counseling, and communication activities throughout the study period.

Researchers are investigating the usefulness of family-based whole-genome sequencing (WGS) to identify cancer predisposition syndromes (CPS) in children and adolescents newly diagnosed with cancer. These syndromes are caused by inherited mutations in cancer predisposition genes and are linked to a higher risk of developing certain cancers. The study aims to understand how often CPS occurs in this population and the impact of germline sequencing on patients and their families. This is a multicenter prospective observational study focusing on clinical benefits and utility of WGS compared to traditional clinical information. Participants will undergo family-based germline whole-genome sequencing to identify genetic variants related to cancer predisposition. The results will be discussed in multidisciplinary meetings, and referrals to Cancer Genetics Clinics for further evaluation and genetic counseling may be recommended. Additionally, the study includes a psychosocial component to assess how the sequencing process affects patients and their families. The study follows patients for up to five years to analyze psychological impact and cost-effectiveness. During the study, researchers will collect detailed family cancer histories and monitor genetic findings, including inherited and new mutations. The primary outcome measures focus on comparing the detection of CPS by WGS versus clinical factors over two years. Secondary outcomes include mutation types, test turnaround times, surveillance adherence, and psychological effects assessed over five years. Participants will be closely followed to evaluate diagnostic accuracy, genetic counseling outcomes, and the broader impact of sequencing on care and family well-being.

Researchers are studying an experimental blood test that detects early tumors in patients with hereditary cancer syndromes. This test, called cell-free DNA (cfDNA) analysis, aims to improve cancer screening by identifying cancer sooner than standard methods. The study compares cancer detection rates and timing between patients receiving cfDNA testing and those receiving regular care, while also exploring the impact on patients' quality of life and psychological well-being. Participants are divided into two groups: the experimental group provides blood samples every four months for four years for cfDNA testing, with results given back to them. Those with positive results will be offered follow-up tests to confirm cancer presence. The control group continues with their usual cancer surveillance without cfDNA testing. Both groups complete questionnaires and interviews to share their experiences and views on the blood test. During the study, participants attend regular blood sample collections, often coordinated with routine clinical blood draws to reduce extra procedures. Researchers measure cancer detection rates over four years and assess if cfDNA testing leads to earlier cancer diagnosis. They also evaluate participants' cancer-related worry, anxiety, and quality of life. The study lasts for four years, with ongoing monitoring and support to understand the test's clinical and personal impact.

Researchers are evaluating a mobile health platform called a chatbot, which uses artificial intelligence and natural language processing to improve communication about genetic testing for hereditary cancer risk. The study focuses on patients at increased risk of familial cancer syndromes in a Medicaid gynecology clinic. The goal is to see if the chatbot can increase recommendations for genetic testing and to understand factors affecting patient access and use of genetic services. Participants will be randomly assigned to either receive the chatbot intervention or usual care. The chatbot starts conversations via text messages to collect personal and family cancer history, identifies high-risk patients using National Comprehensive Cancer Network (NCCN) criteria, provides pre-test genetic counseling, and notifies clinicians to recommend genetic testing. The usual care group will have clinicians collect family history during visits and recommend testing based on NCCN criteria. Genetic testing orders are completed by clinicians for interested patients in both groups. During the two-year study period, participants will be monitored for the proportion recommended genetic testing and the proportion who complete testing. Researchers will assess barriers and facilitators related to inequities in genetic service utilization. Data will be collected through chatbot interactions, clinician evaluations, and follow-up. The study is sponsored by Weill Medical College of Cornell University and aims to improve hereditary cancer risk assessment in an underserved population.

RASopathies are a group of genetic conditions caused by changes in genes related to the Ras/MAPK pathway. People with these conditions may experience developmental challenges, cognitive disabilities, poor growth, birth defects, and have a higher risk of certain cancers. Researchers are studying how genes and environmental factors contribute to cancer development and other health issues in people with RASopathies to improve early detection and prevention. Participants include children and adults diagnosed with or suspected to have a RASopathy, as well as their family members. The study involves collecting medical histories, reviewing medical records, and obtaining biological samples such as blood, urine, saliva, and cheek cell samples for genetic testing. Some participants may undergo additional tests like skin biopsies, physical exams by specialists, imaging scans including CT, ultrasound, bone density, MRI, and other functional tests. Consent is obtained for specific procedures as needed. Participation lasts indefinitely, with occasional follow-up visits or contacts by phone or mail. Researchers will monitor participants’ clinical features, cancer development, and other related health manifestations over time. The study also maintains a biospecimen repository for future research and aims to identify new features linked to RASopathy genetic variations. Outcome measures include ongoing clinical, genetic, and environmental evaluations.

This research aims to evaluate if the Nest software platform can improve cancer screening and care in young adults who have a genetic risk for cancer. The study focuses on whether using Nest helps patients better understand their cancer risks, feel less psychological stress, share risk information more with family and doctors, and keep their care plans up to date. The trial involves comparing patients who use Nest to those who do not. The Nest platform integrates genetic data into patient care through tools for both clinicians and patients. Clinicians use the Nest Care Studio to manage genetic information and order personalized care plans, while patients access the Nest Patient Navigator on mobile devices to store results, understand risks, follow care recommendations, and share information with relatives and other doctors. The study includes two groups: a control group receiving standard genetic counseling and an intervention group using Nest alongside counseling. Both groups complete surveys after visits, and patients follow recommended screening and care plans. Participants will have a genetic counseling or follow-up visit, complete post-visit surveys, and those in the intervention group will use the Nest Patient Navigator. Researchers will assess knowledge of cancer risks, psychological distress, information sharing, and adherence to care plans using multiple measures shortly after visits. The study also tracks clinician use of Nest features and guideline-based care. Participation lasts through the visits and follow-up recommended care, aiming to improve long-term management of hereditary cancer risk.

Researchers are studying genetic factors and molecular pathways involved in various genitourinary cancers, including kidney, prostate, bladder, testis, and penile cancers. These cancers represent a significant portion of cancer diagnoses and deaths in the United States. The study aims to understand the differences between normal and cancerous tissues, investigate gene and protein markers, and examine responses to current and new treatments. The research also includes quality of life studies in men with prostate cancer and explores inherited conditions linked to increased cancer risk. Participants include individuals with biopsy-proven or suspected malignant genitourinary diseases, those with known or suspected inherited cancer disorders, and family members related by blood to affected individuals. Blood and urine samples may be collected, and tissue samples—both benign and malignant—may be obtained during clinically necessary surgeries. The study involves genetic sequencing and molecular analysis of collected specimens, with ongoing investigations into gene mutations and biochemical pathways. During participation, patients will be seen at the Urologic Oncology Branch, where samples will be collected and stored for research. Participants may be contacted if findings relevant to their health arise, with the opportunity for further evaluation. The study involves ongoing assessments of quality of life and molecular genetic outcomes. Participation includes signing informed consent, and the study accommodates both adult and pediatric patients, tracking molecular and clinical data over time.

Researchers are collecting and storing data, tissue samples, and personal and family histories from patients being screened for colorectal cancer and endometrial cancer during routine clinical care. The study aims to discover new genetic mechanisms and proteins related to hereditary cancer syndromes to help develop targeted therapies and prevention strategies. It also focuses on understanding how the immune system can recognize and attack tumor cells carrying mutations. Participants include those with hereditary cancer syndromes undergoing endoscopy or surgical procedures, both with and without treatment using NSAIDs, as well as average-risk individuals undergoing routine lower gastrointestinal procedures. Tissue samples such as normal mucosa, polyps, adenocarcinomas, and blood are collected during standard care procedures like endoscopy, surgery, transvaginal ultrasound, hysteroscopy, and endometrial biopsy at Weill Cornell and New York Presbyterian Hospital. Participants provide informed consent to allow collection and storage of clinical data including demographics, medical history, and outcomes. Samples are processed and stored for future research. The study will monitor novel genetic predispositions, potential therapy targets, and immune responses over a period of seven years to create a valuable hereditary colorectal and endometrial cancer registry and tissue repository.