Wunder Means Miracle

The Wunder Project is a movement created by one doctor and one patient. A movement to get every person involved to change the face of cancer. Contrary to popular belief, it can be cured. The only thing standing in the way between patients and a cure is money, bureaucracy, and politics. The Wunder Project is creative, forward-thinking, and aggressive. The Wunder Project will not back down until we have raised every last cent of the $250 MILLION DOLLARS NEEDED FOR THE CURE and we will ensure that the process will not be held up by inefficiency, middlemen, or red tape. Yes, finding the cure will be nothing short of miraculous. But this is a miracle that we can achieve and a miracle from which we can all benefit. YOU CAN BE PART OF THAT MIRACLE. EVERY PERSON, EVERY DOLLAR, EVERY DISCUSSION COUNTS. You were born to kick cancer’s ass – join Dr. Lenz and Gloria in their mission to cure colon cancer. CANCER, YOUR TIME IS UP.

A CURE FOR COLON CANCER?
How can we cure something when we don’t understand what it is?


The first step: understanding cancer. We need to characterize colon cancer and its subgroups by utilizing comprehensive molecular technologies including analysis of DNA, RNA, miRNA and Methylation to understand what makes a tumor behave in a certain way. Our analysis will be linked to outcome: why one tumor behaves in one way and why a different tumor behaves in a different way.

Our initial goal: to analyze the tumor in the best and most comprehensive way possible, select the most successful and least toxic treatment, understand what makes the tumor unique, and apply the newest medication in development much earlier and based on rational design at each treatment decision (including at time of diagnosis, at time of tumor progression, at time of recurrence). Once we can characterize tumors and their behavior, we can revolutionize the way colon cancer is treated.

The next steps: a multi-pronged approach at finding the cure for colon cancer. Yes, finding the cure will be nothing short of miraculous. But this is a miracle that we can achieve and a miracle from which we can all benefit. YOU can be part of that miracle. Every person, every dollar, every discussion counts. You were born to kick cancer’s ass – join Dr. Lenz and Gloria in their mission to cure colon cancer.

Selecting better and more effective existing treatments for individual patient based on the genetics of the individual tumor and the genomic background of an individual patient, and after comprehensive molecular analyses of 4,000 patients’ tumors to identify molecular signatures for prediction and prognosis.


In addition, we will establish a Tumor Registry and screening for 3,000 patients with collection of tumor tissue, blood and plasma. Patients will have mutational screening conducted on their specific tumor and physicians will be informed about what trials are available for each patient based on his/her tumor’s molecular characterization. We will follow up with these patients and validate/confirm molecular findings identify in the clinical trial cohort (working with NCI, SWOG and EORTC).

The general scientific community currently treats patients based on the early diagnostic tissue of a tumor (initially removed in surgery and biopsied) and not the newer tumor (current tumor after first line of chemotherapy or subsequent surgery), not reflecting the biology of it and how it’s changed. We need to establish a comprehensive database on tumors which have been treated and biopsy them again – after the first line of treatment, after surgery, after recurrence.


Our Approach
Analyzing tumor prior to chemotherapy and at time of progression during lines of therapy. Establishing and identifying mechanisms of escape and emerging subclones of cells surviving treatment. Using single cell molecular analyses to characterize subclones of cells at time of diagnosis that could be responsible for ultimate drug failure.

At the same time, and as part of the overall goal of understanding the driver mutations of a tumor, we need to establish explant cohorts of mice. Through studying the behavior of tumors in mice, we can establish and identify the mechanism of the tumor and how it escapes/overcomes chemotherapy – and apply those findings to the patient. In addition, it saves the patient from having multiple biopsies, which is often not feasible and, with the explant cohort, not necessary.


Our Approach
Establish explant models with all subgroups of colon cancer to characterize the heterogeneity of colon cancers, the mechanisms of actions/resistance to available chemotherapies, the molecular signatures’ predictive value, the escape mechanisms of cancers to therapies, and develop and test novel therapies.

Tumors are heterogenous – every cell in the tumor has different properties, and it’s only a subset of cells in the tumors that actually determine how long a patient with live. There is evidence in the history of cancer treatment: if we treat patients with same chemo on the first line, cells that survive are fundamentally different. The old theory was that tumors developed “acquired resistance,” but this is incorrect thinking. These cells that survived were always resistant to the initial line of chemotherapy – these are cells with root/stem-cell like features, quite different from the cells that died on the first line of chemotherapy.


Our team at Norris has already started a project on single cell molecular characterization at the time of diagnosis in order to be able to identify the problematic cells at the time of diagnosis. These are the cells that we need to focus on — not the cells killed by the first line of treatment, but the cells that resist and overcome chemotherapy and regenerate or recur.

We need to determine what drives these stem-like cells, the cells that don’t die on the first line of treatment – the root of the cancer – and develop drugs that inhibit driver mutations. We need to differentiate these cells and develop smarter chemotherapy drugs that can attack and destroy them.

We will then identify molecular signatures in patients who develop colon cancer and develop novel prevention strategies. Utilizing the largest multi-ethnic cohort and the largest colon cancer family registry in the world, we will identify molecular pathways leading to cancer development and develop preclinical and clinical models to test novel prevention strategies including novel drug development.


Our ultimate goal: to develop the drugs and discover the drug combinations that can cure each subset of colon cancer for current patients, and to develop drugs that can potentially prevent the initial onset of colon cancer for at-risk individuals.

FUNDING THE PROJECT, FUNDING THE PLATFORMS
We are dedicated to putting every cent raised toward The Wunder Project directly toward clinical research and advancements in securing the cure for colon cancer. Funding for overhead and administrative costs will be fundraised for separately and through The WunderGlo Foundation.


That means you can be sure that every single dollar committed to The Wunder Project will be going to Dr. Lenz and his team in order to fund the project, platform by platform, in an organized and efficient manner. This ensures the fastest path to the cure. That’s what Gloria needs and that’s what millions of patients worldwide need.

ROADMAP TO THE CURE
Our gifted team will employ a multi-faceted approach to finding the cure. We have outlined the crucial clinical and research-related steps necessary to making essential advances along with organizational and infrastructure-related enhancements that will help us efficiently and effectively achieve our goals. This is our plan. These are our platforms to the cure.

Create an annotated tumor bank — an infrastructure designed to bank and process tumor specimens for clinical tests that can guide medical decisions; obtain uniform consent for tissue and blood banking for every patient treated at Norris; annotate the tumor bank to include all patient data including ultimate outcomes and post-treatment results; apply whole genome sequencing, exon sequencing, RNA sequencing and mutation spectrum.


Centralizing collection of patient biospecimens (tumor samples, blood, etc.) to profile genes and proteins (genomics, proteomics) and identify mutations that can guide personalized treatment decisions and predict therapy-related toxicity to improve overall patient outcomes.

Estimated Cost: $25M
Timeline Projection: 2 years

Establish a multi-disciplinary tumor board to discuss complex molecular data sets to identify the best treatment strategies including molecular modeling, chemotherapy strategies and surgical options to individualize the treatment plan for patients.


THIS MILESTONE HAS BEEN COMPLETED!

Integrate bioinformatics in analyzing and implementation of predictive molecular signatures into clinical practice


Estimated Cost: $10M
Timeline Projection: 2 years

Conduct molecular characterization/classification of 3,000-4,000 samples from patients with newly diagnosed colon cancer treated with FOLFOX/FOLFIRI/ Bevacizumab(Avastin)/ Cetuximab(Erbitux) and identify molecular signatures associated with response to therapy, mechanisms of resistance and prognosis.
What this means: we take a tumor, isolate the RNA and DNA, entire genetic and genomic characterization, measure important genes, any DNA alteration, see if any pattern of expression or mutation will predict response or efficacy of specific treatments OR predict bad or good outcome – we’ll see a pattern: for example: whatever we do, patients will live X years; another example: when there is this pattern, this drug doubles life expectancy, etc. This will provide essential knowledge about tumors and their behavior.
Timeline Projection: 1 year
(Molecular classification (3,000-4,000 samples) will be efficiently completed since Norris/our team currently has access to the necessary samples.)


Identify ethnic-specific molecular signatures and differences associated with different outcome and toxicities.
Timeline Projection: 1 year

Validate these signatures to predict outcome in prospective clinical trials.
What this means: When you find the pattern even in 3,000-4,000 tissue samples, it is not enough to put it into clinical practice. These findings need to be validated by an independent set. We accomplish that through clinical trials and the patient registry.
Timeline Projection: 1-5 years

Establish patient registry, consisting of 3,000 patients.
What this means: We will collect tissue/blood/serum/urine from a number of patients as identified by The Wunder Project medical team and partners, we do the screening and put them into clinical models and we follow up with these patients for as long as they live. With the tissue acquired in the patient registry, we can validate what we learned with the tissue samples. Our findings and their treatment implications, once confirmed by the patient registry, will come clinical practice everywhere.
Timeline Projection: 3 years

Develop hypothesis driven clinical trials to prove findings or results identified in the clinical and pre-clinical models including to identify subsets of colon cancer associated with prognosis, metastatic pattern, sensitivity to chemotherapy, risk for recurrence, and develop predictive models to select the most effective available chemotherapy regimen for patients.
Estimated Cost: $75M
Timeline Projection: 2-3 years

To develop pre-clinical [animal] models to validate and confirm clinical associations and establish inherited vs. acquired resistance to available chemotherapy options and test novel anticancer compounds based on the molecular profile of the tumor.


What this means: based on promising data in vitro (cell lines), the usual next step to better understand molecular changes and drug sensitivity is using an animal cohort (mice). These mice get a tumor either from a patient or implanted cancer cells. These animal experiments include a control arm (no treatment) and the testing arm (testing a new drug or combination of drugs). Animal studies will also allow us to use genetic alteration of the mouse to study the importance of this gene and to alter genetic make-up of the tumor to study the mechanisms of resistance to the new drug.

Estimated Cost: $20M
Timeline Projection: 2-3 years

Expand animal cohort to establish mechanism for sensitivity and resistance, to test new drugs or drug combinations and discover the subset of patients most likely to respond to the therapy.


Estimated Cost: $10M
Timeline Projection: 2 years

Identify/Design/Screen for novel compounds which not only inhibit molecular targets but molecular pathways driving cancer growth and progression. Collaborate with drug discovery group, chemists who will develop and refine drugs that will be used in clinical trials based on the discovery of driving pathways in colon cancer at the time of diagnosis and progression.


Estimated Cost: $100M
Timeline Projection: 2-5 years

Develop novel educational models including patient advocacy and social media outlets to provide increased access for diverse patient populations to these new treatment opportunities.


Estimated Cost: $10M

THE MEDICAL TEAM PROJECT TIMELINE
Multidisciplinary Tumor Board Established
May 28, 2013


In just three short months since its inception, The Wunder Project can already check off one of its proposed platforms, and ahead of schedule! We have successfully established a multi-disciplinary tumor board, a group of visionary physicians including oncologists and surgeons committed to providing personalized treatment plans for individual patients. This group will discuss complex molecular data sets to identify the best treatment strategies for patients, which could include molecular modeling, various chemotherapy regimens, and surgical options to offer the best possible outcomes for patients.

The multi-disciplinary tumor board consists of the following individuals:

Heinz-Josef Lenz, M.D.
Syma Iqbal, M.D.
Anthony El-Khoueiry, M.D.
Afsaneh Barzi, M.D.
Dilip Parekh, M.D.
Rick Selby, M.D.
Tse Fong, M.D.
Yuri Genyk, M.D.

Sue Martin, M.D.
Vinay Dudalwar, M.D.
Anthony Senagore, M.D.
Jeffrey Hagen, M.D.
Daniel Oh, M.D.
James Buxbaum, M.D.
Suisuie Song, M.D.
John Vallone, M.D.

Lydia Petrovic, M.D.
Phillip Cheng
Joerg Zehetner, MD
Stephen Gruber, M.D.
Gregory Idos, M.D.
Kevin McDonnell, M.D.
Kyle Cologne, M.D.
Andreas Kaiser, M.D.

Achieving this milestone, completing one of our eight enumerated platforms to the cure, is an indication of what will follow from The Wunder Project. We are committed, focused, and ready to end this disease. Cancer, your time is up.