Lecture 24 Cancer s Cure Why do Elephants Rarely get Cancer Elephants have 100X more cells than we do Thus 100X more opportunities to develop a cancerous cell Only 3 of elephants die from cancer compared to 11 25 of people Peto s Paradox Little relationship exists between body size and cancer rates among animals P53 Guardian of Genome and elephant Elephants have 20 copies 40 alleles of p53 Elephant blood cells go through apoptosis at higher rates than human cells when exposed to DNA damaging ionization radiation May be preference toward cell death versus repair to insure no proliferation of P53 Mild physiological stress cell cycle arrest DNA repair cell cycle DNA damage restart P53 severe stress apoptosis How Does Cancer Develop Cancer is a population of prolific competitive successful cells that damage tissue and tissue function by the nature of the cells being so prolific Increased chances for mutations Underlying cancer is changes in genes Changes that cause unregulated cell division Chances that allows proliferation of damaged DNA Changes keep occurring and the environment of our bodies constantly selects for Increased chances for further mutations cells with combination of key genetic changes along with MANY ineffective changes that allow very successful continued growth Cancer is a Growing Snowball of Genetic Changes Cancer is a succession of genetic changes Each time a change confers an advantage in growth those cells and their unique combination of genetic mutations increase in abundance Then another genetic change occurs conferring another advantage in growth And Until cancer cells are equipped for optimal growth in their established so on environment Know Your Enemy There are many ways to negatively affect the cell We know a lot more than we did in the past But Importantly Genetic changes underlies a species survival adaption Genetic change species creation and survival Genetic change cancer Cancer has been around before dinosaurs mutations are dangerous but life is set up to allow mutations to happen Should we truly expect to eradicate cancer No two cancers are exactly alike and in fact often large genetic diversity even exists among cells within a tumor Is there ONE cure A silver bullet Standard Cancer Treatment Regime Our standard cancer treatments largely developed without knowing underlying biology of cancer but were a result of a diligent hunt for the cure and pretty effective For decades people didn t know what drove cancer but they knew it when they saw it and they wanted to get rid of it Surgery Radiation Chemotherapy History of Cancer 1846 First public demonstration of ether was the extraction of a tumor modern era of surgery begins 1880 s radical mastectomy 1903 5 years after Marie Curie discovers radium first treatment of cancer with radiation brachytherapy most commonly used 1947 First remission childhood leukemia using chemotherapy aminopterin 1949 First chemotherapy drug mustard gas approved by FDA Treatments Surgical Surgical removal of tumor or part of tumor A K A Resection total or partial Treatments Chemotherapy Chemotherapy Treatment of cancer with one or more drugs that are cytotoxic and focus on cells in tumors chemotherapeutic agents as part of a standardized regimen 2 types Traditional which kills rapidly dividing cells indiscriminately and targeted antibody therapy The original chemotherapy was a derivative of mustard gas used in WW1 Mustard gas was a powerful suppressor of blood production During WW2 Yale researchers gave venous injections of nitrogen mustards to lymphoma patients with temporary but remarkable results More Chemo Details There are over 100 different drugs available to treat cancer Each has different properties and functions for destroying cancer cells Alkylating agents destroy the DNA of a cell to prevent it from reproducing Anti tumor antibiotics destroy the enzyme a cell needs to reproduce its DNA Anti metabolites act as analogs to mimics of essential nutrients and poison Mitotic inhibitors usually plant derived prevent cells from obtaining the protein needed for survival Combination therapy 3 4 drugs at once is common to reduce drug resistance cells Routes of administration Pill intramuscular injection IM intravenous and efficacy administration IV Treatments Radiation Radiation therapy medical use of ionization radiation Damaged DNA of cells Induces apoptosis Not specific Given in fractionated doses Measured in units of Gray Effect is cumulative Radiation Treatment Planning In radiotherapy radiation treatment planning is the process in which a team consisting of radiation oncologists radiation therapist medical physicists and medical dosimetrists plan the appropriate external beam radiotherapy or internal brachytherapy treatment technique for a patient with cancer Intent is to maximize tumor damage and minimize impacts on healthy tissue Radiation affects cancer and normal cells normal cells recover Treatment Intent Combined modality drugs other cancer treatments radiation surgery Most cancers are now treated in this way Advantage is minimizing chances of resistance developing to any one agent Neoadjuvant preoperative treatment designed to shrink the primary tumor thereby rendering local therapy surgery or radiotherapy less destructive or more effective Adjuvant Postoperative treatment can be used when there is little evidence of cancer present but there is risk for recurrence This can help reduce chances of relapse It is also useful in killing any cancerous cells that have spread to other parts of the body This is often effective as the newly growing tumors are fast dividing and therefore very susceptible Palliative given without curative intent but simply to decrease tumor lod and increase life expectancy For these regimens a better toxicity profile is generally expected Maybe not CURE but Cures Development of more therapies may rely on weakening the cancer cell s unique advantages that allow tumor growth and progression Not a War but a Series of Skirmishes Every cancer is unique with many types of genetic changes Every cancer is dynamic with changes occurring even as we treat it Likely many of us will continue to depend on a growing number of combination of therapies and treatments specific to our disease and win Prevention and Management Inhibit growth What IF elephants smoked and ate twinkies What IF we manage cancers Observe and respond Choose lifestyle to optimize bodies natural responses to cancer cells Less stress
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