Leading Edge of Cancer Research Symposium
This symposium will discuss emerging concepts across the breadth of cancer research from COVID-19 to cancer biology and therapeutics. The event is offered at no charge and is open to research colleagues worldwide.
For the first time, the annual GAP Conference will be held as a virtual event. This conference is a forum where MD Anderson and its global network of hospitals, health systems and research institutions collaborate to develop impactful, innovative ideas and research that help MD Anderson achieve its mission to end cancer globally. The 2020 conference centers on the theme "New Frontiers – Leading Inspired Cancer Care." Conference registration is free.
John H. Blaffer Lecture Series
Join us each week from September through May as an internationally recognized scientist presents his or her latest results. The Blaffer Lecture Series is coordinated by MD Anderson's Genetics department.
Connect Science Seminar Series
The Connect Science Seminars seek to connect basic and translational cancer researchers in Houston, Texas, and the nation during the COVID-19 pandemic. This series is open to all, and will showcase outstanding scientists at major institutions in the U.S. and elsewhere every Thursday.
ENJOY SCIENCE Seminar Series
The ENJOY SCIENCE seminar series is open to internal and external colleagues and patients from around the world. Join us on Tuesdays, Thursdays and Fridays, as we highlight the incredible clinical and mechanistic research taking place at MD Anderson.
A new data analysis tool developed by researchers at The University of Texas MD?Anderson Cancer Center incorporates a user-friendly, natural-language interface to allow biomedical researchers without specialized expertise in bioinformatics or programming languages to conduct intuitive analysis of large datasets.
The open-access, artificial intelligence (AI)-driven program, called DrBioRight, was created to lower barriers for all researchers to make full use of the increasingly large amounts of data generated in modern research methods. A report of this platform was published today in Cancer Cell.
“We felt that we could improve the current model for conducting routine bioinformatics analysis and greatly speed up turnaround time by creating a tool that any researcher could use,” said Han Liang, Ph.D., professor of Bioinformatics and Computational Biology. “Our long-term goal for DrBioRight is to be an intelligent collaborator for every researcher.”
High-throughput technologies used in modern biomedical research generate large, complex datasets that provide comprehensive information about patients, animal models or cell lines being studied. These may include, for example, studying the whole of genetic information (genomics), gene expression (transcriptomics), or protein expression (proteomics).
Because these “omics” datasets are so complex, it can be challenging to answer specific biological questions without specialized analytical approaches, explained Liang. These analyses are usually done with using a computer script written in a variety of programming languages, which requires some understanding of both programming and bioinformatics.
Bioinformaticians can help to navigate and process these complex datasets, but the work can be time consuming. Therefore, the research team developed DrBioRight to enable researchers to more easily conduct routine analyses of their own data through a user-friendly chat interface with natural-language interactions.?
The natural language-oriented program allows users to ask questions of the program as if they were speaking naturally rather than in complex programming languages, explained Liang.
DrBioRight is freely available to academic researchers. Initially, the program has a number of modules ready-built to handle the most common types of bioinformatics questions and includes some of most frequently used public cancer datasets available, such as The Cancer Genome Atlas and Cancer Cell Line Encyclopedia.
As a confirmation of the approach, the researchers replicated the analysis of a classic cancer genomics paper using DrBioRight and found it to accurately reproduce the previously published results.
Because the program is driven by AI, it also has the ability to learn from each inquiry and improve analysis, becoming a more useful tool over time. Going forward, the researchers hope to improve DrBioRight to enable users to analyze their own datasets as well as allow open development for new modules.
“As we work to improve the program, we also want to enable other bioinformaticians to contribute their algorithms and teach DrBioRight,” said Liang. “Involvement from the entire research community will help to create a tool that is useful in answering complex research questions more efficiently.”
This research was supported by the National Institutes of Health (U24CA209851, U01CA217842, P50CA221703 and P30CA016672), the MD Anderson Faculty Scholar Award to Liang and The Lorraine Dell Bioinformatics for Personalization of Cancer Medicine Program.
Additional collaborators include: Jun Li, Ph.D., Hu Chen, Yumeng Wang, Ph.D. and Mei-Ju May Chen, Ph.D., all of Bioinformatics and Computational Biology. H. Chen and Y. Wang also are members of the graduate program in Quantitative and Computational Biosciences at the Baylor College of Medicine, Houston, TX. A full list of author disclosures can be found with the full paper here.
The University of Texas MD Anderson Cancer Center and Taiho Pharmaceutical Co., Ltd., today announced a three-year strategic collaboration to accelerate the development of treatments for significant unmet medical needs in oncology, including patients with brain metastases and those with cancers refractory to available therapies.
This collaboration will bring Taiho’s unique portfolio of preclinical and clinical brain-penetrant therapies together with both the translational research capabilities of MD Anderson’s Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform as well as insights and clinical development infrastructure from MD Anderson’s Brain Metastasis Clinic.
“Our collaboration with MD Anderson exemplifies a direct line of sight from target development to therapies for patients with limited treatment options,” said Teruhiro Utsugi, Ph.D., managing director at Taiho. “Investigating our novel portfolio of drug candidates in this innovative research structure will enable us to more rapidly identify and develop effective treatment strategies.”
According to the American Brain Tumor Association, metastases to the brain and spine are diagnosed in more than 200,000 patients annually in the US. However, the development of effective treatment approaches for these patients has been hampered because they often are excluded from clinical trials. However, recent studies in melanoma, lung and breast cancers have demonstrated that patients with brain metastases can gain significant clinical benefit from immunotherapy and targeted therapies, leading to improvements in quality of life and survival.
MD Anderson’s Brain Metastasis Clinic is a patient-focused, multidisciplinary center designed to reduce the time from a diagnosis to treatment for patients with brain metastases while improving access to clinical trials. The TRACTION platform, an industry-scale translational research unit within MD Anderson’s Therapeutics Discovery division, has established a robust integrated research framework with the Brain Metastasis Clinic to identify innovative treatment approaches and execute novel clinical trials.
“MD Anderson’s commitment to delivering novel therapeutic strategies to patients with unmet clinical needs is exemplified in the development of the Brain Metastasis Clinic and its close collaboration with the TRACTION platform,” said Timothy Heffernan, Ph.D., executive director of TRACTION at MD Anderson. “Our alliance with Taiho combines outstanding drug discovery with expertise in translational research and clinical development to advance new treatment options for patients diagnosed with brain metastases.”
Results from a Phase II trial led by researchers at The University of Texas MD Anderson Cancer Center suggest that a combination of ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) can generate durable responses in a subset of patients with metastatic castration-resistant?prostate cancer?(mCRPC), an “immune-cold” cancer that does not typically respond well to immunotherapy.
In a cohort of patients without previous chemotherapy treatment, the overall response rate (ORR) was 25% and median overall survival (OS) was 19 months. In a post-chemotherapy cohort, the ORR was 10% and media OS was 15.2 months. Four patients (two in each cohort) achieved a complete response.
The results of the CheckMate 650 trial, published today in Cancer Cell, are the first report of combination immune checkpoint inhibitors in mCRPC. Early results from this study were presented at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium. Based on the findings, alternate dosing regimens are now being evaluated in an expanded clinical trial to reduce treatment-related toxicities.
“Historically, prostate cancer has been very resistant to checkpoint inhibitors because it is immunologically cold with few tumor-infiltrating T cells,” said principal investigator?Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology. “These results suggest that a combination approach to increase T cell infiltration and then block inhibitory pathways may be a useful strategy for treating these patients. Going forward, we plan to optimize the schedule and dosing to improve the safety profile.”
Designing a combination strategy
In previous research published in Nature Medicine, Sharma and colleagues discovered that prostate cancers deploy multiple mechanisms to dampen the anti-tumor immune response. Although anti-CTLA-4 therapy could recruit T cells, the tumor-infiltrating T cells elicited compensatory inhibitory pathways, including immune-suppressing proteins PD-L1 and VISTA.
This would explain why previous clinical trials evaluating single-agent checkpoint inhibitors have not been effective in treating patients with mCRPC, said Sharma, who co-directs MD Anderson’s immunotherapy platform, part of the institution’s Moon Shots Program?.
The researchers hypothesized that combining anti-CTLA-4 (ipilimumab) with anti-PD-1 (nivolumab) may be effective in bringing T cells into the tumor and overcoming the resulting immunosuppressive response.
The multi-institution, open-label study enrolled 90 men with mCRPC, who received the combination therapy every three weeks. Patients were enrolled in two cohorts: one with and one without prior chemotherapy. Participants were 77.8% Caucasian, 10% Black/African-American and 12.2% other.
In addition to response rates, the combination therapy achieved disease control in 46.9% and 13.3% of patients, with a median progression-free survival of 5.5 and 3.8 months in the pre- and post-chemotherapy cohorts, respectively.
Despite the positive responses, grade 3 and 4 treatment-related adverse events occurred in 42.2% of pre-chemotherapy patients and 53.3% of post-chemotherapy patients. The most common of these events was diarrhea, pneumonitis, colitis and increased lipase. Treatment-related adverse events led to discontinuation of therapy in a total of 31 patients. There were four treatment-related deaths, two in each cohort.
“There were patients who had clear benefit as a result of treatment, but there also were patients who had serious adverse events, which led us to amend the protocol to evaluate alternate schedules and doses and improve the safety of this approach,” said Sharma.
Based on these data, the trial has been expanded to include more than 400 patients, with different dosing and schedules to identify strategies that can improve efficacy and minimize toxicities.
Exploring biomarkers associated with response
The researcher team also conducted analyses to identify potential biomarkers associated with clinical outcomes in these patients.
While this study represents a small number of patients, their findings suggest that the combination may be more effective in patients with a relatively high tumor mutational burden (TMB). This is in agreement with previous work that suggests certain patients with mCRPC may respond to checkpoint blockade despite having low TMB relative to other cancers, such as melanoma and lung cancer.
“The current study represents the first step in trying to identify mCRPC patients who would benefit from combination therapy with ipilimumab plus nivolumab based on chemotherapy exposure as well as preliminary biomarker analyses,” said co-author?Sumit Subudhi, M.D., Ph.D., assistant professor of?Genitourinary Medical Oncology. “The data generated to date are encouraging, but we clearly have more work to do in the expansion cohort as we try to administer effective combination strategies with fewer toxicities.”
This study was supported by Bristol-Meyers Squibb and ONO Pharmaceutical Company, Limited. Sharma is a member of the Parker Institute for Cancer Immunotherapy (PICI) and co-director of PICI at MD Anderson. A full list of authors and their disclosures can be found with the paper here.