Controlling a Killer Malfunction

By: Brady Sebo, Tom Fish, Addela Marzofka, and Colton Cummings

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Big Picture

• About 1.2 million people are diagnosed with cancer each year.

• Cancer happens by invading their cells and causing corruption in the nuclei, and sometimes is caused by cells going bad not always for a particular reason.

• A mutation in the cells DNA.

Cancer Statistics

• 1 in 3 people contract cancer and 1 in 4 people die from it.

• 7.9 million people died because of cancer related causes in 2007.

Causes• A person’s heredity, age, and different

carcinogens they are exposed to, can cause cancer.

Age

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Heredity/DNA

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Carcinogens• The term carcinogen refers to any substance,

radionuclide or radiation that is an agent directly involved in the promotion of cancer or in the increase of its propagation (reproduction).

Tobacco

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Potato Chips

Cancers

• Many cancers can’t be avoided, but some can.• Throat and mouth cancer is mainly caused by

chewing tobacco.• Lung cancer is usually caused by smoking.

Types of Cancer

• Lung, tongue, brain, bladder, breast, colon, rectal, kidney, skin, leukemia, prostate,

thyroid, and pancreatic, and many more.

Breast Cancer Cell

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Lung Cancer Cell Dividing

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Cancer Causes

• Varies for types of cancer• Main ones include- Chronic Fatigue, Persistent

Cough, Coughing Blood, Sore Skin, Persistent Sore Throat, and Change in Bladder Habits.

Different Ways Of Controlling Cancer

• Extracellular Antibodies• Intracellular Antibodies• Monoclonal Antibodies

Extracellular Antibodies• Example- Chemo Therapy • Extracellular antibodies have been used to

refer to an antibody that works outside the cell to cure cancer and other diseases.

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Intracellular Antibodies

• Intracellular Antibodies have been used to refer to an antibody that works within the cell to bind to an intracellular protein. Due to the lack of a reliable mechanism for bringing antibodies into the cell from the extracellular environment, this typically requires an antibody within the target cell, which can be accomplished by gene therapy.

Monoclonal Antibodies• They are directed towards antigens and they

are used to prevent the rejection of transplanted organs. It is reasonable to expect similar new drugs in the future.

• Monoclonal Antibodies don’t have many side effects because it is directed toward exactly defined antigens.

• Examples- Drip IV’s, pills.

Drip IV

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Pills

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Monoclonal Antibodies

•

EGFR

Extracellular Receptor

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Intracellular Receptor

Our Goal

• Our goal was to model the EGFR protein to attain a better understanding of how the the drug, lapatinib, fits into the receptor to inhibit the cancer.

Rasmol

This is a picture of the atom

in molecular

form.

This is a model of the

drug lapatinib. It fits into the molecule to help inhibit the cancer.

EGFR• Cells divide when they receive signals. One of

these signals is called Epidermal Growth Factor (EGF).

• They are received by the Epidermal Growth Factor Receptor (EGFR).

• This is what starts cell division.

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Human Epidermal Growth Factor Receptor

EGFR

• EGFR is a receptor enzyme, and a intercellular tyrosine kinase domain.

• It transfers phosphate groups from ATP to specific target molecules.

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Understanding EGFR

• These tyrosine kinases roles are growth, differentiation, metabolism, adhesion, motility, and death.

Here are cells expressing the epidermal growth factor receptor after a short incubation with complexes of epidermal growth factor EGF and Quantum Dots (QD, red) nanoparticles. (Max Planck)

Max Planck Institute for Biophysical Chemistry

Understanding EGFR

• The addition of a phosphate to a polar group of amino acid residue is called phosphorylation.

• This turns a hydrophobic portion to a hydrophilic portion which changes the structure of the protein.

Phosphorylation• This plays a regulatory role in the signaling by

turning EGFR “on” and “off”.

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Signaling and Cancer

• In a cancerous cell the pathways receiving the signals are always on.

• The cell then divides uncontrollably, causing a tumor.

Cell Dividing Uncontrollably

Tumor on Healthy Cell

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Drugs and EGFR• The breast cancer drug called Lapatinib

interacts with EGFR.• Lapatinib interferes with the EGFR signals,

slowing down cell division.

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Lapatinib in the treatment of Breast Cancer

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EGFR Importance

• EGFR is important in the fight against cancer because it can possibly help slow down the division of cells and almost completely stop the advancement of the cancer to other parts of the body.

Acknowledgements

• We would like to thank Dr. Shannon Colton, all of the people of the Center for Biomolecular Modeling at the Milwaukee School of Engineering and Mr. Heeren.