1. Develop disease models
  2. Create repositories of disease models
  3. Create a Biobank
  4. Characterize the anal cancer genome

Build pre-clinical tools that enable and speed subsequent research1

Accelerate trial recruitment to rapidly realize the clinical benefit of the above activities4

  1. Incentivize researchers
  2. Seek out and identify new collaborative
  3. Initiate projects
Research Roadmap
  1. Conduct empirical in-vitro screens
  2. Rationally test agents

2Test drugs in preclinical models of HPV-related cancer, providing the rationale for clinical trials

3Fund investigator research

  1. Mitigate challenges
  2. Clinical trial recruitment
  3. Streamline and accelerate the flow

The current drug development system is not optimized for speed. The existing medical research model is built upon a system of competition for grants and awards, not getting new drugs to patients as quickly as possible. The results of the existing model show its obvious flaws: HPV-related cancer patients are still often faced with treatment protocols first administered in the 1970s.

Our Foundation is 100% funded by private donors who believe in our singular focus to eliminate anal caner and all cancers caused by HPV – as quickly as possible. Our biggest asset is our freedom to identify and pursue development of the tools that can overcome the barriers to drug discovery. By aligning incentives across all of the relevant stakeholders (including pharma, academic institutions, governments, cancer specialist organizations, payers and, most importantly, patients and their families) and fostering collaboration amongst them, we can leverage the collective power of a multitude of brilliant minds.

Developed with the input of the Foundation’s Scientific Advisory Board and Michael Milken’s drug discovery think-tank, FasterCures, and informed by our personal, heartbreaking experience with the disease, the following Research Roadmap is our plan to advance development of effective treatments for anal and all HPV-related cancers.

1. Build pre-clinical tools that enable and speed subsequent research.

Build pre-clinical tools that enable and speed subsequent research1

a.Develop disease models including cell lines, patient-derived xenografts and genetically engineered mouse models.

b.Create repositories of disease models to make them easily accessible to the research community.

c.Create a Biobank to provide a centralized source of high-quality biospecimens linked to clinical data.

d.Characterize the anal cancer genome and determine key differences between HPV+ and HPV- specimens. Investigate mutation similarities between oral, anal and cervical cancers.

Research Roadmap Step 1
  • Develop disease models including cell lines, patient-derived xenografts and genetically engineered mouse models.
  • Create repositories of disease models to make them easily accessible to the research community.
  • Create a Biobank to provide a centralized source of high-quality biospecimens linked to clinical data.
  • Characterize the anal cancer genome and determine key differences between HPV+ and HPV- specimens. Investigate mutation similarities between oral, anal, and cervical cancers.

2. Test drugs in preclinical models of HPV-related cancer, providing the rationale for clinical trials

2Test drugs in preclinical models of HPV-related cancer, providing the rationale for clinical trials

a.Conduct empirical in-vitro screens of diverse compound libraries – including all approved drugs, preclinical pharmaceutical collections, and publicly available compound collections – and test the most active compounds in in-vivo models.

b.Rationally test agents that inhibit identified therapeutic targets in in-vitro and in-vivo models.

Research Roadmap Step 2
  • Conduct empirical in-vitro screens of diverse compound libraries – including all approved drugs, preclinical pharmaceutical collections, and publically available compound collections – and test the most active compounds in in-vivo models
  • Rationally test agents that inhibit identified therapeutic targets in in-vitro and in-vivo models

3. Fund investigator research

Fund investigator research3

a.Incentivize researchers to focus on HPV-related anal cancer by offering peer-reviewed seed grants to test hypotheses, and generate preliminary data needed to obtain larger funding sources.

b.Seek out and identify new collaborative models of translational research that aim to chaperone the best ideas in the lab to the clinic as quickly as possible.

c.Initiate projects that aim to bring together a fragmented community, to discuss and disseminate the latest and most novel approaches to preventing and treating anal cancer (e.g. developing consensus guidelines for anal cancer diagnosis and initial stage, radiation techniques and IMRT, surveillance recommendations, QoL).

Research Roadmap Step 3
  • Incentivize researchers to focus on HPV-related anal cancer by offering peer-reviewed seed grants to test hypotheses and generate preliminary data needed to obtain larger funding sources.
  • Seek out, identify and support new collaborative models of translational research that aim to chaperone the best ideas from the lab to the clinic as quickly as possible.
  • Initiate projects that aim to bring together a fragmented community, to discuss and disseminate the latest and most novel approaches to preventing and treating anal cancer (e.g. developing consensus guidelines for anal cancer diagnosis and initial stage, radiation techniques like IMRT, surveillance recommendations and quality of life).
  • Partner with other funders including the NIH, academic institutions and foundations to leverage resources in order to answer as quickly as possible whether proposed therapies work.

4. Accelerate trial recruitment to rapidly realize the clinical benefit of the above activities

4Accelerate trial recruitment to rapidly realize the clinical benefit of the above activities

a.Mitigate the challenges of clinical trial recruitment – 85% of all clinical trials face delays and 30% never get off the ground due to lack of volunteers.

b.Clinical trial recruitment is a particular challenge in rare cancers.

c.Streamline and accelerate the flow of clinical trial participants in a new tool called HPVTrialFinder and speed progress toward preventative and therapeutic breakthroughs for all HPV-related cancers.

Research Roadmap Step 4
  • Mitigate the challenges of clinical trial recruitment – 85% of all clinical trials face delays and 30% never get off the ground due to lack of volunteers
  • Clinical trial recruitment is a particular challenge in rare cancers
  • Streamline and accelerate the flow of clinical trial participants through a new tool called HPVTrialFinder and speed progress toward preventative and therapeutic breakthroughs for all HPV-related cancers

Immortal Anal Cancer Cell Line Competition ($100,000)

Cell lines are critical for understanding cancer and developing new treatments. Researchers have been working on cervical cancer cell lines for many decades, and more recently, oral cancer cell lines. However, there are no successfully validated anal cancer cell lines. After careful assessment of the disease landscape and consultation with numerous key opinion leaders, we understand that the lack of anal cancer cells prevents many researchers from undertaking basic and translational projects in this field.

A fundamental question in the research community is to what extent are HPV-related anal, oral and cervical cancers related? Would they respond to the same treatment? If so, under what conditions? To answer this, we first need to develop the preclinical tools to do the appropriate studies.

Our goal is to develop five successfully validated and well-characterized anal cancer cell lines in the next 24 months, each of which represents the biology of the tumor from which it was derived. In order to achieve this aim, we must encourage as many labs as possible to focus on the problem. Working with an organization that has a proven track record in accelerating immortal cell line development, the Rare Cancer Research Foundation (RCRF), we will offer $20,000 for each valid line that is submitted to the ATCC, a private, nonprofit biological resource center and research organization. The competition is worldwide and we will work to ensure that the tissue, once banked, is available internationally.

This type of format is a win-win: the prize is only given if a validated cell line is developed, and the researcher gets a financial incentive for the work done. The global availability of the prize encourages greater collaboration than could be achieved through a grant to a specific laboratory or institution and the success payout eliminates the risk of funding research that fails to produce. This model also encourages novel and creative approaches to establishing new cell lines. Once the line has been validated and stored, the public, academics, research labs, biotech and pharmaceutical companies have access to this tool.

Anal Cancer Genome Project ($200,000)

The trend in modern cancer drugs is to target and kill cells that harbor specific mutations. All cancers are the result of DNA mutations that permit uncontrolled cellular growth. Knowing what mutations are present across HPV-related cancers of any site will be critical to identifying generalizable treatments.

Recent, technological advancement has enabled scientists to sequence all DNA (including mutations) in a cell very rapidly. The anal cancer genome project is the logical next step following the thorough mapping of squamous cell carcinoma of both the head and neck, and the cervix.

Characterizing the anal cancer genome (both HPV+ and HPV-, Cancer Genome Atlas [TCGA] study) in a similar fashion would further highlight the similarities and differences between HPV-related cancers of different body parts. An essential study, which could be administered separately, would involve commissioning a researcher to compare and analyze the results of the sequencing amongst cervical, anal and oral cancers (and others if they are available). Common mutations between all sites would warrant further investigation.

As long as the data generated from this project are made freely available, we do not have a preference where the research is carried out. We are familiar with the Wellcome Trust Sanger Institute in the UK as a leading cancer genomics center.

Drug Repurposing and Screening Project ($500,000)

We want advancement in treatment options that benefit all HPV-related cancer patients. Clinical trials that recruit HPV-related cancer patients tend to offer repurposed drugs originally designed for use in another cancer or anatomical site or slightly tweak old protocols. Such approaches are unlikely to generate progress in outcomes for patients suffering from HPV-related disease.

Repurposing old drugs or testing new compounds in a clinical setting is extremely uncertain, time-consuming and costly. The purpose of the Foundation’s drug-screening program is to test entire libraries of compounds in a more cost-effective, preclinical environment (starting with those 3,000 drugs which have already been approved for use in other applications) for maximum clinical benefit. Following the direction of our Scientific Advisory Board, we believe the optimal candidate for a high-impact drug (e.g. that would be powerful enough to treat systemic disease) would be one that demonstrates preclinical benefit in all body parts affected by HPV. Following the HPV-related cancer cell line screen, the compounds that show the greatest activity will progress to the next stage of the drug development process with transgenic and xenograft models.

Our hope is that we identify at least 50 promising treatments of which we have not yet obtained clinical data. Results from this screening would create the impetus to begin clinical or animal trials.

HPVTrialFinder ($500,000)

85% of all clinical trials face delays and 30% never get off the ground due to lack of volunteers. This is a particular challenge for less common or fragmented diseases. Under-enrollment slows the progress towards breakthroughs in anal cancer and HPV-related cancer research.

An HPVTrialFinder would streamline and accelerate the flow of clinical trial participants. It is designed to provide trial coordinators improved efficiencies in connecting with potential participants, as well as provide patients with a way to identify HPV-related trial opportunities.

Using an algorithm that we license from a third-party or create ourselves, we intend to match volunteers to trials for which they may qualify (e.g. based on area, demographic, and medical history). Volunteers and trial teams can use the portal to communicate with one another and learn more.

We imagine that other countries will also utilize and feed trials to the portal. Trial teams can review de-identified profiles to pre-screen candidates once they have entered an anonymous profile. Email alerts go to both trial teams and volunteers once a match has been identified. Match criteria include medications, supplements, side effects, pre-existing treatment, age, surgical procedures and genetic markers.

To further develop this tool, we must review at least 20 trial protocols from industry and academia to establish the most useful data points for pre-screening. Registering volunteers also requires awareness building and education about trials. This tool will require two full-time employees managing outreach, strategy, working with trial teams, and travelling to patient events/investigator meetings. It would also require back-end digital support and a significant investment in the technology.

When addressing metastatic, systemic or recurrent disease, trials focus on one body part instead of all the parts affected by the carcinogenic virus, HPV. Our view is that a breakthrough in one systemic HPV-related cancer will be a breakthrough in all HPV-related cancers. Issues with patient accrual could be overcome if trials were designed to recruit anal, cervical, oral, vaginal, vulvar and penile patients simultaneously.

International Rare Cancer Initiative Anal Cancer Guidelines ($100,000)

Our Scientific Advisory Board has highlighted that one of the major challenges in treating anal cancer patients is that there are few up-to-date guidelines sponsored by the international research community. We have previously provided a seed grant to the International Anal Neoplasia Society to disseminate the clinical consensus about AIN (anal intraepithelial neoplasia) and who, when and how to screen patients for anal cancer. The grant provided start-up capital and resources to the new society, which develops administrative support to develop international, consensus guidelines for anal cancer diagnosis, staging, radiation techniques, surveillance and Quality of Life. These guidelines will be based on input of all the investigators and will be submitted for publication.