Cancer Program Overview

Cancer: Are we closer to a cure? Jesse Boehm, Ph.D. Broad Institute of Harvard and MIT Cambridge, MA 1/11/08 Cancer is a huge public health problem Overall mortality rates have not changed for cancer… 700 Deaths per 100,000 people 600 500 400 300 200 100 0 586.8 1950 245.8 193.9 194.4 2001 Heart Disease Cancer * Age-adjusted to 2000 US standard population. Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised. 2001 Mortality Data–NVSR-Death Final Data 2001–Volume 52, No. 3. http://www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_03.pdf But we have made HUGE advances in some cancers!!!! Before Iressa treatment After 3 months of Iressa treatment Image provided by B. Johnson We have made HUGE advances in prevention!!!! The Fundamentals of Cancer What is cancer? Molecular causes of cancer How faulty genes are involved How a cancer cell becomes dangerous What is Cancer? •An uncontrolled growth of cells •A genetic disease •A family of similar diseases newscenter.cancer.gov An Uncontrolled Growth of Cells non-dividing cells normal skin skin cancer dividing cells structural support ..... ..... ..... .. .. . . .. ... .. . .. . •Healthy cells turn into the enemy •divide too quickly or abnormally •become abnormal shapes and sizes •grow in all directions •Cells stop listening to the body, which is telling them to stop! A Genetic Disease Normal Cells Cancer Cells ..... ..... ..... •Mutations in DNA can make normal cells become cancerous •These can be inherited or spontaneous A Family of Similar Diseases •Carcinomas: from cells which protect the body from air and internal fluids •Sarcomas: from cells in supportive tissue •Leukemias and Lymphomas: from cells in the blood and immune system newscenter.cancer.gov The Fundamentals of Cancer What is cancer? Molecular causes of cancer How faulty genes are involved How a cancer cell becomes dangerous Common causes of cancer •Chemicals (e.g. tobacco, asbestos) •Viruses (e.g. HPV) •Radiation from the sun What do all of these have in common? They all lead to MUTATIONS in the DNA of your cells They are called MUTAGENS Can also be predisposed to getting cancer by inheriting mutations from parents newscenter.cancer.gov Smoking and Alcohol Cigarette smoking causes 87 percent of lung cancer deaths and is responsible for most cancers of the larynx, oral cavity and pharynx, esophagus, and bladder Tobacco smoke contains thousands of chemical agents, including over 60 substances that are known to cause cancer. Alcohol use has been implicated in the development of a number of cancers • Risk increases >1 drink for women or 2 drinks for men/day Causes of Cancer What are mutations and how do they cause normal cells to become cancer cells? Cancer Cells How Could a Mutant Protein Make Cells Divide Out of Control? ? mutant DNA mutant protein cancer cells The Cell Cycle Controls Cell Division Cells divide (mitosis) Cell Cycle Growth Growth DNA Synthesis The Cell Makes Sure That There are no Problems Did division go correctly? Am I ready to divide? Cell Cycle Am I big enough? Is my DNA copied correctly? The Cell Cycle Has Checkpoints Did division go correctly? Am I ready to divide? Cell Cycle Am I big enough? Is my DNA copied correctly? The Normal Protein Functions at a Cell Cycle Checkpoint Cell Cycle Is my DNA copied correctly? Normal Protein The Mutant Protein Allows The Cell to Divide Out of Control Cell Cycle go! Normal Protein I can’t stop and check if the DNA has been copied correctly!!! Abnormal/ Mutant Protein The Fundamentals of Cancer What is cancer? Molecular causes of cancer How faulty genes are involved How a cancer cell becomes dangerous How Faulty Genes are Involved Not every gene leads to cancer when mutated Mutations in two specific categories of genes can lead to cancer • Tumor-Suppressor Genes Oncogenes • How Faulty Genes are Involved Not every gene leads to cancer when mutated Mutations in two specific categories of genes can lead to cancer • Tumor-Suppressor Genes Oncogenes • Inactivated Tumor Suppressor Genes Lead to Cancer •Tumor Suppressor (TS) genes normally inhibit cell growth cell •Mutations in TS genes may inactivate them, so that they cannot stop cell-growth TS gene •TS genes include p53 and BRCA1/2 How Faulty Genes are Involved Not every gene leads to cancer when mutated Mutations in two specific categories of genes can lead to cancer • Tumor-Suppressor Genes Oncogenes • Activated Oncogenes Lead to Cancer •Oncogenes normally promote cell growth carefully cell oncogene •Mutations in oncogenes may over-activate them, so that they always promote cell-growth •One well-known oncogene is called RAS Mutations in Specific Genes Turn a Normal Cell into a Cancer Cell Mutate tumor suppressor genes, turning these genes OFF Mutate oncogenes, turning these genes ON 1 2 3 4 5 6….. mutations normal cell cancer cell The Fundamentals of Cancer What is cancer? Molecular causes of cancer How faulty genes are involved How a cancer cell becomes dangerous Benign vs. Malignant Benign: A non-malignant tumor lacking the ability to invade surrounding normal tissue Malignant: A tumor that tends to grow, has the capacity to invade nearby tissue and spreads through the blood stream adapted from “Concise Dictionary of Biomedicine and Molecular Biology,” Pei-Show Juo, 1996 How cancer cells become dangerous •A cancer cell on its own will not cause you harm •To become the disease “Cancer” the cell must: •1) Form a tumor (at least) •2) Recruit a blood supply = angiogenesis (solid tumors only) •3) Spread to other parts of the body = metastasis (advanced stages) Metastasis Cancer cells enter blood vessels Cells travel through the blood stream to distant sites Cells then invade new tissues, and begin to grow Cancer treatment Heart Lung Tumor There are different types of treatments Drugs (chemotherapy) Radiation Surgery Cancer can be local or metastatic local (one primary tumor) metastatic (secondary tumors) Cancer therapy: local and systemic Rx LOCAL: surgery and radiation SYSTEMIC: chemotherapy, etc. Why need targeted therapy? The problem of Selectivity of chemotherapy and radiation normal cells cancer cells Why need targeted therapy? The problem of Selectivity of chemotherapy and radiation normal cells cancer cells Why need targeted therapy? The problem of Selectivity of chemotherapy and radiation normal cells cancer cells Killing a fly with a cannon ball? We can kill the fly but… Problem with selectivity leads to side effects  SIDE EFFECTS! normal cells cancer cells • • • • hair follicles: hair loss bone marrow:  immune defense, anemia, clotting problems gut lining: diarrhea skin: flaky/scaly skin How can we improve cancer therapy? Pick a better TARGET! Normal cell Cancer cell Points to remember Cancer is a family of similar diseases, not just one!  Different cancers have different causes, treatments and outcomes Cancer is caused by MUTATIONS • Prevent your exposure to mutagens! A tumor causes a patient harm by becoming malignant and metastasizing By learning more about cancer we are developing new, “smarter” cancer drugs  More effective  Fewer side effects Thank you!