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Tim Heffernan, P., Joseph Marszalek, P., Virginia Giuliani, P., & Spencer, N. (2019, November 8). MD Anderson Cancer Cener. Retrieved from Youtube: https://www.youtube.com/watch?v=fKOTzMPxREQ

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How MD Anderson’s TRACTION Platform is accelerating drug development

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Alice for Achiever (Executing)- This individual would assist with getting the work done and will take great satisfaction from producing quality work.

Andrew for Activator (Influencer)- I have been called an influencer on my job. This person can read people well and can corral the group and get buy into a project.

Chelsea for Command (Influencer)- This person will take charge and lead the group. This person is different from the Achiever, who prides themselves in producing quality work. The Commander has vision but may not know how operationalize the vision. Carter for Communication (Influencer)- This person is good at putting words into action. The communicator would work with the achiever who is good at getting the work done.

Daisy for Developer (Relationship builder)- will help keep the entire group together. Help each to see the qualities they bring to the group to get the work done.

Andrew would be my team lead. He is a good judge of people and knows how to get buy in from everyone in the group and express how everyone in the group is integral in getting the project or task complete.

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I have been working at MD Anderson for greater than 12 years, spending the majority of that time as a Stem Cell Transplant Nurse. Most of our patients were part of targeted therapy trials and came to our floor once traditional curative modalities which included chemotherapy, radiation and proton therapy depending on the type of cancer had been exhausted. I have witnessed firsthand how targeted therapies have saved some and have had some casualties but not from the cancer but most times of the opportunistic infections that followed therapy. For the patients that targeted therapy helped, for those who attended their daughter or son’s graduation or wedding, and for those who paid it forward through donations of time or money, I would say targeted therapy is wonderful and have given hope to many.

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MD Anderson Making Cancer History: Traction Platform is accelerating drug development.

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A translational platform addressing key challenges in oncology drug development. The group of researchers combine biology and chemistry, conduct experiments internally and partner with external researchers to find the right drug for the right patient. The targeted population of patients are patients with no traditional treatment options, they need specific targeted therapies which is the whole premise of the TRACTION Platform

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Discovering and developing new treatments for cancer is a difficult process with many obstacles. These challenges can slow the process of bringing new therapies to patients. That's why MD Anderson built the Therapeutics Discovery division, to overcome these hurdles.

This unique team of physicians, researchers, and drug discovery and development experts collaborates across the institution to advance new therapies, providing unique insights that can help with drug development.

MD Anderson's extensive clinical and laboratory research infrastructure enables the team to efficiently advance new medicines from the discovery phase all the way into clinical trials. They have successfully developed a number of new therapies, including recent progress on treatments for certain patients with leukemia, lung cancer, liver cancer, and head and neck cancers.

New targeted therapy enters clinical trial for advanced lung cancer and other solid tumors

A new drug targeting a protein called SHP2 has entered a Phase I clinical trial for patients with advanced lung cancers and other solid tumor types driven by gene mutations that activate the MAPK signaling pathway -- notably KRAS, EGFR and others.

The drug, known as BBP-398, is being developed in collaboration with Navire Pharma, an affiliate of BridgeBio Pharma, Inc. It was initially discovered and developed by scientists in the Institute for Applied Cancer Science (IACS) and Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platforms, both part of the Therapeutics Discovery division.

Many therapies used to treat solid tumors target components of the MAPK signaling pathway, but cancers often become resistant to these drugs. A preclinical study led by Therapeutics Discovery and Navire scientists found that SHP2 inhibitors were effective in blocking the MAPK pathway and overcoming resistance to available therapies.

"Because SHP2 works downstream in these pathways, targeting this protein makes an attractive treatment strategy for patients with lung cancer who are no longer responding to treatments like osimertinib," says Yuting Sun, Ph.D., co-project lead and senior research scientist with TRACTION. "We are eager to see how this new drug performs in clinical trials and to continue advancing it for patients in need of better treatment options."

The Phase I study is designed to determine the correct treatment dose for future trials and evaluate the safety and activity of this therapy in patients with advanced cancers with mutations in MAPK signaling. David Hong, M.D., is leading the clinical trial.

First-in-class therapy for patients with liver, head and neck cancers

Working in collaboration with Ionis Pharmaceuticals, the Therapeutics Discovery team is using a different approach to target previously undruggable biological pathways in difficult to treat liver cancers. This approach relies on an antisense oligonucleotide (ASO), which is a small piece of synthetic genetic material rather than a classical chemical drug compound. The ASO are able to block the activity of target genes inside a cancer cell and stop the proteins from being made.

Working closely with Ionis and other MD Anderson researchers, members of the TRACTION platform have helped to advance an ASO that targets YAP1, which regulates cell growth and survival. YAP1 is overactive in several cancer types, including liver cancer and certain head and neck cancers with a specific genetic mutation.

Laboratory experiments show that the ASO targeting YAP1 is effective in treating these cancers in animal models. Based on those promising preclinical studies, the therapy has now entered a Phase I clinical trial at MD Anderson, led by Timothy Yap, M.B.B.S., Ph.D.

"This antisense oligonucleotide represents a novel, first-in-class therapeutic option, and we hope that it will prove to be a promising new treatment for patients with tumors driven by high YAP1 activity," says Tim Heffernan, Ph.D., executive director of TRACTION.

Creating new targeted therapies for patients with genetically defined leukemias and lymphomas

While our genes are passed onto us by our parents, the epigenome is a set of instructions for the cell laid on top of our genes. These chemical modifications help control gene expression, like a light switch and dimmer. Disruptions to the epigenome are a hallmark of cancer development, so targeting epigenetic functions are an attractive target for cancer therapies.

Therapeutics Discovery scientists are actively working to develop a new targeted therapy against an epigenetic regulator protein called CBP/p300. This protein is responsible for cancer development in certain patients with early onset acute myeloid leukemia and diffuse large B cell lymphoma.

"We recognize these patients do not currently have effective treatment options available to them. We are actively working to advance a CBP/p300 inhibitor that we hope will lead to an impactful new medicine," says Phil Jones, Ph.D., vice president of Therapeutics Discovery.

The work to develop this new therapy is supported by The Mark Foundation for Cancer Research, who recently launched a Drug Discovery Partnership with IACS. This new targeted therapy is expected to enter clinical trials in 2021 and could represent the first CBP/p300 inhibitor to be clinically tested in these patients.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.

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Discovering and developing new treatments for cancer is a difficult process with many obstacles. These challenges can slow the process of bringing new therapies to patients. That's why MD Anderson built the Therapeutics Discovery division, to overcome these hurdles.

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Department of Theraputics

Executive Director of Traction Platform Tim Heffernan, Ph.D.

Institute Head of Traction Platform Joseph Marszalek, Ph.D.

Principle Institute Research Scientist of Traction Platform Virginia Giuliani, Ph.D.

Institute Associate Scientist IV of Traction Platform Nakia Spencer

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People who have exhausted all traditional therapies can participate in targeted therapies combining chemistry and biology to find medications based on anatomy that will respond to their cancer.

Provide hope to patient and family.

Helping in making Cancer history

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Side effects from chemotherapy targeted therapy:

Vomiting

Diarrhea

Anorexia

Alopecia Areata

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A translational platform addressing key challenges in oncology drug development. The group of researchers combine biology and chemistry, conduct experiments internally and partner with external researchers to find the right drug for the right patient. The targeted population of patients are patients with no traditional treatment options, they need specific targeted therapies which is the whole premise of the TRACTION Platform

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MD Anderson’s TRACTION Platform is accelerating drug development

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How MD Anderson’s TRACTION Platform is accelerating drug development