Skip to Content
COVID-19 Resources
Translational Research Program (TRP)
Contact CIP
Show menu
Search this site
Last Updated: 10/10/18

SPORE in Skin Cancer

Wistar Institute/University of Pennsylvania

Principal Investigator:
Meenhard Herlyn, DVM, DSc

Principal Investigator Contact Information

Meenhard Folkens Herlyn, D.V.M., D.Sc.
Caspar Wistar Professor in Melanoma Research
Director, The Wistar Institute Melanoma Research Center
Professor, Molecular and Cellular Oncogenesis Program
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104
Tel: (215) 898-3950
Fax: (215) 898-0980


The intent of the Penn/Wistar SPORE in Skin Cancer is to decrease the morbidity and mortality of skin cancers through the development of targeted therapies. This SPORE investigates three major skin cancers — melanoma, cutaneous T cell lymphoma (CTCL) and squamous cell carcinoma (SCC). The projects and cores focus on the leading cause of skin cancer deaths, melanoma. Our overarching hypothesis is that maximal long-lasting clinical impact achieved by interfering with signaling pathways and/or stimulating the host immune response requires that we take into account tumor-specific and host-specific genetic and epigenetic signatures. Each of the four projects has clear translational objectives and specific hypotheses that rest on a solid body of preliminary studies. The three cores support the projects and the developmental research and career developmental programs.

The first overall objective is to develop novel therapies in melanoma. In three of the four projects, we propose clinical trials of advanced metastatic melanoma with the overall hypothesis that melanoma is not a homogenous disease and, therefore, should be treated with different strategies. Projects 1 and 2 capitalize on our previous findings that two of the major druggable resistance mechanisms to BRAF inhibition in BRAF-mutant melanoma are activation of PI3K signaling and autophagy. Project 1 (Herlyn/Schuchter) proposes extensive tissue-based studies to understand the effects of concurrently targeting mutant BRAF and PI3K. We expect the combination to be more effective in killing tumor cells and preventing or extending recurrence in a large subset of patients. Project 2 (Amaravadi/Speicher) combines autophagy and BRAF inhibition in patients with BRAF-mutant melanoma, and identifies other effective targeted therapy and autophagy inhibitor combination strategies that have future development potential for BRAF wild-type patients. Project 4 (Vonderheide/Kalos/June) deals with immunotherapy of melanoma by adoptive transfer of lymphocytes that are engineered to bind to tumor cells. The project is built on highly encouraging data from other malignancies that show activated T cells can achieve effective tumor regression and lasting clinical responses.

The second overall objective is to establish new biomarkers in advanced melanoma. We hypothesize that identification of meaningful biomarkers not only will increase our knowledge of the dynamics of disease regression and progression before, during, and after therapy, but also will directly impact the management of the disease by tailored selection of therapy for patients, improved assessment during therapy, and enhanced outcome prediction. In projects 1 and 2, we will analyze patients' melanomas for genetic abnormalities with the intent of stratifying them prior to initiation of therapy into at least five different disease groups that will dictate therapeutic decision-making. We also will determine whether therapy-related changes can be detected in the sera (Project 2), tumors (Projects 1 and 2), and/or blood (Project 4) of patients.

Finally, Project 3 (Nathanson/Kanetsky) is a genome-wide association study that will investigate inherited genetic susceptibility to acute toxicities and outcomes of immunostimulatory therapy using the anti-CTLA4 drug, Ipilimumab. Here we expect to discover novel genetic signatures that may, after further study, facilitate identification of patient subgroups to help tailor therapeutic decision-making.

We expect that this highly interactive SPORE program will yield tangible results for clinical practice in melanoma and other cancers of the skin.


Co-Leaders & Co-Investigator:
Meenhard Herlyn, D.V.M, D.Sc.
Lynn Schuchter, M.D.
Katherine Nathanson, M.D.


The long-term objective is to optimize the effectiveness of BRAF inhibitors in the treatment of BRAF mutant melanoma and thereby improve the outcome and survival for patients with advanced melanoma. Mutated BRAF is a relevant therapeutic target in approximately 50% of all melanomas. Targeted therapies have been successfully developed against proteins in the MAPK signaling pathway, BRAF inhibitors being the most effective to date. Clinical trials using two different inhibitors of the mutant BRAF protein (vemurafenib [Vem] and dabrafenib) have achieved unprecedented single-agent response rates of 50-60% in patients with BRAF-mutant melanomas with significant improvements in survival. However, nearly all patients with BRAFV600E mutant melanomas eventually become resistant to BRAF inhibitor therapy, with inevitable tumor progression and death due to metastatic disease. Recent reports from a number of groups, including our own, have identified multiple mechanisms of intrinsic (primary) and acquired (secondary or adaptive) resistance to BRAF inhibition, often involving the PI3K (phosphoinositol 3 kinase) pathway.

Our overall hypothesis is that effective combination therapies using BRAF inhibitors will improve clinical outcomes for patients with mutant BRAF metastatic melanoma.

We have prioritized co-inhibition of the PI3K pathway based on extensive evidence for its constitutive activation both in preclinical models of resistance and in patients’ melanomas. To achieve our goal, we will investigate an irreversible pan-PI3K inhibitor (PX-866), which ranked as one of the top PI3K inhibitors in our preclinical studies, in combination with the BRAF inhibitor Vem in both preclinical models and a clinical trial in patients. Demonstrating the safety and efficacy of combination therapy with BRAF and PI3K inhibition will build a foundation upon which to develop additional combination therapy strategies. The identification of biomarkers related to response and resistance in individual patients will serve as a basis for personalizing the selection of combination therapy. Our preliminary studies suggest the important role of PI3K pathway activation in diminishing response to single agent Vem and also the involvement of PTEN (phosphatase and tensin homolog) mutations or deletions in conferring resistance. Since PI3K activation is expected to be present in patients and is one mechanism of resistance to BRAF inhibition, this provides a strong rationale for combination therapy with a PI3K inhibitor.

Specific Aim 1: Combine BRAF inhibitors with PI3K inhibitors to treat patients with BRAF mutant melanoma.

  1. Investigate biomarkers associated with combined BRAF and PI3K inhibition.
    We hypothesize that specific PI3K signaling pathway alterations in melanoma patient-derived tumor specimens will be related to response to therapy. We will collect both archived tissue and serial tumor samples from subjects enrolled on an ongoing biospecimen-intensive phase II trial for genetic/genomic and protein expression (RPPA, IHC) analyses. In this subaim, we will evaluate whether PTEN status (based on mutation/deletion, and protein expression) or other genetic/genomic or protein changes involving the PI3K pathway are associated with progression-free survival (PFS) by determining the molecular and protein expression profiles of pre-treatment, and on-treatment tumor biopsy samples.
  2. Investigate the mechanisms of resistance to combined BRAF and PI3K inhibition.
    Our preclinical and early clinical data suggest that the BRAF/PI3K combination, while effective, is not curative. Thus in this subaim, we will identify mechanisms of resistance to the combination therapy using tumor cells from biospecimens collected from patients before combination therapy, two weeks after the onset of therapy, and upon detection of resistance (progression). We will use patient-derived cells grown in culture and patient-derived xenografts (PDX) as pre-clinical models of resistance. Using genetic/genomic and protein expression data (RPPA), we will investigate effectors involved in resistance, with particular focus on the PI3K and MAPK pathways. Validation of these mechanisms will be performed in matched serial biopsies from patients.

Specific Aim 2: Develop therapeutic strategies for mutant BRAF melanoma cells that are not fully eradicated upon combination to BRAF and PI3K inhibitors.

The heterogeneity of melanoma indicates that the combination of BRAF and PI3K inhibition will not be equally effective for all patients. We will therefore develop novel strategies to treat mutant BRAF melanomas resistant to the BRAF and PI3K inhibitors, the goal being the eradication of any surviving tumor cells. We will first focus our efforts on evaluating a BRAF/MEK/PI3K triple combination using cell-line-based xenografts and PDX models that have been established from biospecimens collected in Aim 1. We will then use screening approaches to combine BRAF/MEK and PI3K inhibitors with novel compounds targeting different pathways and melanoma effectors. This screening will be conducted on genetically diverse melanoma subtypes extending beyond mutant BRAF melanomas. Validation of the most effective triple combination will be carried out in cell line-derived xenografts and PDX models derived from the patients' tumors from Aim 1A. These studies will provide the foundation for future clinical trials.

The goal of this proposal is to maximize the clinical benefits of BRAF inhibitors in patients with BRAF-mutant melanomas by developing combination therapies that can result in long-lasting responses and improved patient survival. To accomplish this goal we will conduct a clinical trial treating patients with a drug combination to simultaneously inhibit mutant BRAF and PI3K, a protein associated with drug resistance and survival of the malignant cells. This proposal will investigate the genetic factors that can predict response or resistance to therapy. Using innovative mouse models and human tumor specimens, we will also test novel combination therapies that can be used in future clinical trials. We expect that this knowledge will help select patients with the greatest likelihood of benefiting from selected drug combination regimens and result in durable responses and increased patient survival.


Ravi Amaravadi, M.D.
David Speicher, Ph.D.


Our long-term objective is to develop new therapies in melanoma that are more effective than the current strategies, which have greatly improved in recent years but are not curative. Our working hypothesis is that autophagy is a suitable therapeutic target in melanoma if inhibited in combination with the right signaling inhibitor(s) and in a subset of melanoma patients that are most likely to respond to this approach. Our preclinical and clinical studies have demonstrated that compared to other malignancies, melanoma is especially reliant on autophagy for survival(1, 2). We have also found that high levels of autophagy predict poor prognosis in melanoma. The next major unanswered question is whether or not high levels of autophagy in melanoma tumors predict a better response to autophagy-directed therapies, making measurement of autophagy levels a potentially useful predictive strategy.

Multiple clinical trials involving hydroxychloroquine (HCQ), which blocks downstream processing of autophagic vesicles (AVs), show promising anti-tumor activity by activating apoptosis. However the best targeted therapy to combine with autophagy inhibition and the best patient subset for this approach remain open questions. In this proposal we will focus first on an investigator-initiated clinical trial combining the BRAF inhibitor vemurafenib with HCQ and then identify novel synergistic combinations worthy of future clinical trials for BRAF wild type melanoma. The vemurafenib and HCQ trial is a natural extension of our preclinical and clinical studies. This proposal will address two critical gaps in current knowledge that are expected to expand the use of autophagy modulation as part of combination therapeutic strategies in melanoma by: 1) developing better molecular tools to noninvasively monitor autophagy levels in patients and 2) characterizing the effects of novel, more potent second generation combination regimens involving autophagy inhibitors.

To address these gaps, candidate autophagy biomarkers that we recently identified in preclinical secretome studies and newly identified candidate pharmacodynamics (PD) biomarkers will be quantitatively analyzed in specimens from a simultaneously conducted clinical trial and a co-preclinical trial in patient-derived melanoma xenografts (PDX) with high versus low autophagy. In addition, we will leverage the SPORE infrastructure to identify the most potent signaling inhibitor-autophagy inhibitor combinations in melanoma. The following two specific aims reflect a bench-to-bedside approach that will have a significant impact on melanoma patient care.

Aim 1. Determine autophagy modulation and anti-melanoma activity of combined BRAF and autophagy inhibition in high versus low autophagy BRAF mutant melanoma.

We will first conduct a phase I trial of HCQ and vemurafenib in advanced BRAF mutant melanoma patients. In parallel we will conduct a preclinical trial using PDX models to test the hypothesis that combined BRAF and autophagy inhibition will produce greater autophagy modulation and antitumor activity in melanomas with high basal levels of autophagy than in those with low levels. If the HCQ and vemurafenib combination is safe in patients, a triple drug combination of BRAF, MEK, and autophagy inhibition will be tested in mice. If this three drug regimen is more efficacious than BRAF and autophagy inhibition alone in mice, it will be incorporated into the trial design for patients. Finally, we will determine if autophagy-related differentially secreted proteins can reliably distinguish high versus low autophagy and therapy-associated modulation of autophagy in clinical and preclinical blood specimens

Impact: This bench-to-bedside-and-back approach is expected to lead to: a) future multi-institution studies to further validate our candidate plasma autophagy biomarkers, and b) randomized studies involving vemurafenib + HCQ with or without MEK inhibition, and non-invasive autophagy related biomarker signatures. Scientific knowledge gained will accelerate the development and clinical testing of next generation autophagy inhibitors.

Aim 2. Identify novel targeted agents that synergize with autophagy inhibition to kill BRAF wild type melanoma cells.

To increase the likelihood of finding the most effective combination of signaling and autophagy inhibitors for patients with NRAS mutant and BRAF/NRAS wild type melanoma, we will conduct a pharmacological synthetic lethal screen. Specifically, HCQ or its more potent derivative, Lys05, will be assayed in combination with clinically viable targeted therapies that will focus on the PI3K/mTOR signaling pathway and other constitutively activated pathways in melanoma. Subsequently, the importance of putative drug targets will be confirmed using a focused shRNA library. The efficacy of these combinations will be validated in tumors from genetically characterized PDX. Finally, we will perform functional validation of pathway modulations of synergistic combinations using global proteomics and phosphoproteome systems biology analysis.

Impact: These findings will be used to design the next generation of clinical trials involving a rationally designed combination involving inhibitors of key signaling pathways and autophagy inhibitors. Completion of these specific aims not only has a high likelihood of identifying effective new combination therapy options for melanoma patients but will also overcome several key stumbling blocks in autophagy research. Future studies will be focused on testing safe and effective combinations identified in this proposal in phase II clinical trials, and further developing clinical biomarker assays that emerge from the experiments in this proposal.

Autophagy is a new therapeutic target in melanoma. Blocking autophagy with chloroquine derivatives could:

a) improve outcomes in patients with advanced melanoma, and b) could lead to improved cure rates in patients with earlier stage melanoma at high risk of recurrence. Completion of this project will identify the best therapeutic combinations involving autophagy inhibitors that will pave the way to achieving these goals in melanoma. Knowledge gained will allow autophagy inhibitors to be used better for other cancers.


Co- Leaders:
Katherine Nathanson, M.D.
Peter Kanetsky, Ph.D.


Marked progress in the treatment of patients with advanced stage melanoma has occurred over the past two years. In particular, ipilimumab was recently approved for use in patients with metastatic disease. Ipilimumab therapy has potential to provide benefit to all melanoma patients because it acts systemically on the innate immune system via anti-CTLA-4 activity. Increased overall survival for patients treated with ipilimumab has reached 10 to 11 months. Further, the survival benefit is observed when ipilimumab is given either as a firstline agent with dacarbazine or as a second- (or greater) line agent in patients who have progressed on other therapies. However, the overall survival at two years is only 24-30%, depending on dose. In addition, grade three or higher immune-related adverse events (irAE) occur in 7 to 25% of patients receiving therapy, again dependent upon the dosage. Currently, it is not possible to determine which patients are most likely to respond to therapy, or delineate those that may be at increased risk for developing irAEs. Thus, it is of critical importance to identify potential genetic markers that can be used for patient selection and risk stratification. Inherited genetic variation plays a role in determining adverse toxicities and outcomes in response to other therapies. Moreover, inherited variation has been shown to play a crucial role in the pathogenesis of autoimmune diseases. Thus, it is likely that inherited variation may play an important role in determining not only who might respond to immunotherapies, such as ipilimumab, but also which patients may be at risk for irAEs. Indeed, variation in CTLA4 itself has been strongly associated (odds ratio (OR) > 4) with response to ipilimumab. Results from a small genome-wide association (GWA) study that examined outcomes related to ipilimumab therapy show exciting potential, and suggest that our project will be successful in identifying novel genetic associations associated with irAE and survival outcomes. Our long term goal is to identify inherited variation that can inform clinical decision making about treatment with ipilimumab. In order to address the question of whether inherited variation is associated with irAEs and tumor outcomes in patients with melanoma treated with ipilimumab, we propose the following studies:

Aim 1: To determine the association of inherited genetic variation and immune-associated adverse events in patients with metastatic melanoma treated with ipilimumab by completing

Aim 1a: Candidate-based gene and pathway analyses of genes involved in lymphocyte activation, cytokines, cytokine receptors and within the MHC region.

Aim 1b: An agnostic genome-wide SNP-based approach.

Using biosamples from patients treated with ipilimumab, we will identify variants associated with grade 3 and higher immune-related adverse events. As ipilimumab acts through immune mediated mechanisms, we will first focus on pathways in which inherited variation already has been shown to play a causative role in autoimmune disorders as well as the important immunologic MHC region. We then will expand our analysis to investigate markers across the entire genome.

Aim 2: To investigate the association between inherited genetics and survival in patients with metastatic melanoma treated with ipilimumab by completing

Aim 2a: Candidate-based gene and pathway analyses of genes involved in lymphocyte activation, cytokines, cytokine receptors and within the MHC region.

Aim 2b: An agnostic genome-wide SNP-based approach.

Using biosamples from melanoma patients treated with ipilimumab, we will identify variants associated with response to therapy. Our approach will be similar to that in Aim 1.

Aim 3: To replicate genomic markers identified in Aims 1 and 2 in an independent sample set of patients treated with ipilimumab and preliminary characterize their potential functional role.

Aim 3a: Replication of variation identified in Aims 1 and 2 as associated with irAEs and survival

Aim 3b: Bioinformatic assessment of genomic markers.

Using an independent set (distinct from Aims 1 and 2) of biosamples from patients treated with ipilimumab, we will confirm our observed genetic associations. Then using publically available online bioinformatics datasets, we anticipate being able to characterize replicated genetic markers in terms of putative biological function.

We anticipate identifying genetic markers associated with immune-related adverse events and survival in patients treated with ipilimumab. Although beyond the scope of this proposal, ultimately we hope that our findings will inform future prediction models that will be useful in helping to target ipilimumab therapy to those most likely to respond and least likely to develop severe immune mediated adverse toxicities.

Ipilimumab is an FDA approved drug for the treatment of metastatic melanoma. Currently no biomarkers are known that predict either response to therapy or immune associated adverse events (irAEs). Based on various lines of evidence, inherited genetic variation may play a role in determining response and irAEs, which we will evaluate in this study. The ultimate goal is to identify markers that allow us to select patients who will derive the most benefit from treatment with ipilimumab.


Robert Vonderheide, M.D., D.Phil.
Carl June, M.D.


Adoptive transfer of autologous T cells modified to express chimeric antigen receptors (CAR) have begun to demonstrate potent activity in a number of pilot clinical trials, including our own. Applying the CAR therapeutic platform to solid tumors such as melanoma is widely considered a major opportunity but also a major challenge and thus the focus of this proposal. We have shown in chronic and acute leukemia that CAR T cells are capable of unprecedented on-target clinical activity (1, 2). We now seek to develop new strategies for CAR T cell therapy utilizing c-Met as a novel target and an mRNA-based cell transduction system in patients with melanoma. This project brings together the skills of three laboratories and a team of clinical investigators to develop, implement, and test next generation CAR T cell strategies in melanoma. Our approach uses advanced genetic T cell engineering with mRNA vectors combined with optimized and clinically relevant cell culture methods and cutting edge and systematic immune assessment as our translational platform. In preliminary work in mice and more recently in humans, we have observed that T cells expressing optimized mRNA CAR constructs exhibit potent anti-tumor efficacy against solid tumors. Preliminary data further show that CAR T cells targeting c-Met, a receptor tyrosine kinase which is markedly overexpressed in melanoma, kill c-Met+ tumor cells in vitro and in vivo. Although recent reports indicate that CAR T cells with transgenes stably expressed with retro- or lentivirus can have “on target” but “off organ” toxicity, CAR expression in our mRNA system is transient. Potentially toxic effects will abate quickly over time, thus providing a built-in safety maneuver. Here, we propose a clinical trial of intratumoral injection of c-Met RNA CAR T cells for patients with metastatic melanoma to understand the potential toxicities and anti-tumor capability of the approach and the prospect that CAR T cell-mediated tumor cell death will trigger a “vaccine” effect in patients and propagate an anti-tumor systemic immune response. We hypothesize that mRNA-based c-Met-specific engineered CAR T cells can be used to trigger anti-tumor immunity and achieve clinically meaningful tumor responses in patients with melanoma without untoward toxicity.

Aim One. Determine the clinical impact of administering autologous c-Met RNA CAR T cells intratumorally in patients with metastatic melanoma

In a phase I dose escalation study, determine the feasibility, toxicity and tumor response following intratumoral injection of autologous c-Met RNA CAR T cells in patients with metastatic melanoma.

Aim Two. Determine the immunological potency and mechanism of c-Met RNA CAR T cells in patients treated in the clinical trial

Understand the immune reaction and other modulations in the melanoma microenvironment following intratumoral CAR T cell injection.

Determine the scope, breadth, and duration of systemic immune responses potentially induced by therapy.

This project aims to develop new immune therapy for patients with metastatic melanoma using engineered T cells specific for the tumor. T cells engineered to express a chimeric antigen receptor specific for c-Met and encoded by mRNA will be tested for safety, efficacy, and mechanism of action in a phase I clinical trial for patients with metastatic melanoma.


Meenhard Herlyn, D.V.M, D.Sc.
Lynn Schuchter, M.D.


The Penn/Wistar SPORE in Skin Cancer Administrative Core A is designed to provide scientific leadership, effective communication, and an administrative support structure to ensure the coordination of all SPORE activities. The essential services provided by the Core include: administrative support for all of the investigators in each project and core; scientific oversight and progress review for each project; coordination of selection processes for the Developmental Research Program (DRP) and Career Development Program (CDP) and streamlining of these investigators and their projects into full SPORE projects as they evolve; fiscal and financial management and oversight for all components of the SPORE; and organization and communication of all SPORE meetings and activities.

The overall objectives of the Administrative Core are to:

  1. Establish and maintain an administrative structure to provide support for and management of all SPORE activities.
  2. Foster an environment to maximize collaborative and translational research among SPORE investigators between Wistar and Penn and between other SPORE and NCI initiatives.
  3. Ensure compliance with all institutional, governmental, and NCI regulations and policies.

Effective administrative management of this SPORE in Skin Cancer is essential for it to successfully achieve its overall goal of improved treatment and quality of life for patients with cancers of the skin.


Co-Leaders and Co-Investigators:
Xiaowei (George) Xu, M.D., Ph.D.
Michael Feldman, M.D.
David Elder, MB, ChB, FRCPA
Giorgos Karakousis, M.D.


The primary objective of the Biospecimen and Pathology Core of the Penn/Wistar SPORE in Skin Cancer is to provide a centralized, high quality core focused on procurement, processing, analysis and distribution of malignant and normal tissue in support of translational cancer research. Core B will support all aspects of the Penn/Wistar SPORE, including funded projects, career development awardees, developmental projects as well as InterSPORE collaborations. The Biospecimen and Pathology Core (Core B) is well equipped to achieve this objective. Core B has readily access to fresh and FFPE melanoma tissues. Over 1000 melanoma specimens are processed annually at Penn and many of the specimens have residual melanoma tissue that can be procured. Core B is led by two senior pathologists who have extensive experience in clinical trial tissue management and bioinformatics. Core B will fully utilize the state-of-the-art tissue banking and informatics infrastructure already established by the Abramson Cancer Center at the University of Pennsylvania (ACC).

This includes the Tumor Tissue and Biospecimen Bank (TTAB), the integrated biospecimen database (Labvantage LIMS database); and the tissue processing and research capacity developed in the Department of Pathology and Laboratory Medicine. Tissue distribution will be governed by the Tissue Resource Allocation Committee (TRAC), which has established clear guidelines in tissue allocation. Core B will function as a hub to procure, process, track, distribute and store well-annotated tissue and blood specimens including quality controls and integration with clinical information. Core B will also provide technical support for developing and performing immunohistochemical and immunofluorescent staining and other tissue-based molecular assays as requested by SPORE projects as well as provide pathologic expertise to individual projects in the interpretation of histological data.

Aim 1. To collect, store, process and analyze biospecimens (blood and fresh and paraffin embedded tissue) of tumor and normal tissue according to the specifications of each SPORE project including inter-SPORE collaborations.

Aim 2. To maintain a well-annotated and high quality tumor bank with attention to tracking, distribution and governance to maximize use, efficiency and patient confidentiality.

Aim 3. To maintain a comprehensive biospecimen database (Labvantage LIMS database) that includes detailed pathologic characteristics linked to essential clinical and genomic data.

Aim 4. To provide technical assistance for tissue related studies and develop new assays needed by SPORE projects as well as expert interpretation of studies performed on the tissues.

The Biospecimen and Pathology Core is a required Core that serves the Penn/Wistar SPORE in Skin Cancer by providing well annotated high-quality biospecimens. The Core will function as a hub to procure, process, track, store and distribute well annotated biospecimens including quality controls.


Leader and Co-Investigators:
Phyllis Gimotty, Ph.D.
Mingyao Li, Ph.D.
Rosemarie Mick, M.S.


The Biostatistics Core (Core C) brings together a team of biostatisticians who have extensive experience with biostatistical methodologies and their application to research studies in cancer of the skin and who have close collaborations with the SPORE project investigators. Core personnel are committed to actively participating with research investigators to address research questions related to each project and to ongoing participation in project meetings and program meetings.

The primary objectives of the Biostatistics Core are to insure that SPORE-related studies will have high-quality study designs and statistical analysis plans that will provide a solid foundation for their statistical inferences band that the statistical analyses will be presented in the most informative manner. To support these objectives, the faculty and staff of the Biostatistics core will provide their expertise and experience in the following areas:

  1. Research methodologies necessary to design and implement rigorous experimental and clinical studies, and collaboration on specific experimental and clinical designs focusing on definition of study populations, measurement issues, potential sources of bias, sample size and power calculations, randomization, and efficient experimental design.
  2. Statistical methodologies critical for the evaluation of each project’s research hypotheses and development of statistical models specified by the research objectives of the SPORE studies, as well as to conduct methodological research to solve practical problems that arise and to conduct discovery studies using archived public databases relevant to the research projects.
  3. Interpretation of research data and collaboration with project investigators to make scientifically and statistically appropriate statements, as well as to assist in the preparation of scientific abstracts, presentations, and manuscripts.

Collaboration between the senior biostatisticians in the Biostatistics Core and the research investigators conducting SPORE-related studies will insure that the SPORE research studies will have high-quality study designs and relevant statistical analysis plans that will provide a solid foundation for each study’s conclusions.