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PowerPoint Slides English Text Brazilian Portuguese Translation

History of Cancer VideoTranscript

História do Câncer Roteiro

Professional Oncology Education History of Cancer Time: 21:28

Educação Para Profissionais em Oncologia História do Câncer Duração: 21:28

Raymond DuBois, M.D., Ph.D. Provost & Executive Vice President The University of Texas, MD Anderson Cancer Center

Raymond DuBois, M.D., Ph.D. Superintendente e Vice-Presidente Executivo

Universidade do Texas, MD Anderson Cancer Center

History of CancerHistory of CancerHistory of CancerHistory of Cancer

History of CancerHistory of Cancer

Raymond N. DuBois, M.D., Ph.D.

Provost & Executive Vice President

Hello, I am Ray DuBois, the Provost and Executive Vice President here at The University of Texas MD Anderson Cancer Center. Today, I will be taking to you about the history of cancer, how it has developed over several 100 years, and what we know about that, and also the important role of research in our future and how we are going to develop new treatments and other aspects of cancer treatment and prevention.

Olá, sou Ray DuBois, Superintendente e Vice-Presidente Executivo do MD Anderson Cancer Center, Universidade do Texas. Hoje, falarei sobre a história do câncer, seu desenvolvimento em centenas de anos e o que sabemos sobre ele e, também, o papel importante da pesquisa em nosso futuro e como desenvolveremos novos tratamentos e outros aspectos do tratamento e prevenção do câncer.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

ObjectivesObjectivesObjectivesObjectives

• Upon completion of this lesson, participants will

be able to:

– Appreciate the scope of cancer in the US population

– Understand how large investments in research may

impact disease

– Appreciate trends in cancer prevention, diagnosis

and treatment

So, the objective of this discussion is going to lead to a better appreciation of a scope of the cancer problem in the U.S. population. Hopefully, we will understand how large investments in research may impact disease, and appreciate the trends that are occurring in cancer prevention, diagnosis, and treatment.

Portanto, o objetivo desta discussão é conduzir a uma melhor compreensão da abrangência do problema do câncer na população norte-americana. Compreenderemos como investimentos de vulto em pesquisa podem afetar a doença e reconhecer as tendências atuais em prevenção, diagnóstico e tratamento de câncer.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

Current Status of Cancer in the USCurrent Status of Cancer in the USCurrent Status of Cancer in the USCurrent Status of Cancer in the US

• Incidence of cancer

– Estimated 1.479 million new cases of cancer were diagnosed

in 2009

– 40% lifetime risk

– Overall decline of 1.1% during 1999-2006 period

• Declined primarily due to decrease in colon and breast

cancer

• Incidence has leveled off for lung cancer in women

• Five year survival rate current 66.1% (1999-2005)

• Mortality rates

– 21% lifetime risk; leading cause of death under the age of 85

– Decline in mortality rates of 1.6% during 2001-2006 period

• Mainly due to lung, breast and colon

www.seer.cancer.gov

Now, if we look at the incidence of cancer in the United States, we estimate almost 1.5 million new cases were diagnosed in 2009 and this amounts to about 40% lifetime risk. Overall, there has been a slight decline of about 1.1% during the period from 1999 to 2006 and this was due primarily to a decrease in colon and breast cancer incidence and mortality, but this has leveled off in women to a certain extent. The five-year survival rate is 66% over 1999 to 2005. In the mortality rates, there is a 21% lifetime risk. It is a leading cause of death from cancer under the age of 85, and there is a decline in mortality. It has been slight, but consistent, especially in lung, breast, and colon.

Agora, se examinarmos a incidência de câncer nos Estados Unidos, estimamos que cerca de 1,5 milhão de novos casos foram diagnosticados em 2009, o que equivale a cerca de 40% de risco para adquirir a doença durante a vida da pessoa (“lifetime risk”). Em geral, houve uma pequena queda de cerca de 1,1% no período de 1999 a 2006 e isto se deve, principalmente, a uma diminuição na incidência e mortalidade de câncer de cólon e de mama, mas até um certo ponto estabilizou-se em mulheres. A taxa de sobrevida em cinco anos é de 66% de 1999 a 2005. Nas taxas de mortalidade, há um “lifetime risk” de 21%. É a causa principal de óbitos de câncer abaixo de 85 anos de idade e há uma queda na mortalidade. Ela foi leve, mas uniforme, principalmente no pulmão, mama e cólon.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

• 70-80 million years ago -- evidence of cancer exists in dinosaur

fossils

• 3000 BC -- evidence of cancer exists in mummies

• 400 BC -- the Greek physician Hippocrates was the first to

recognize the difference between benign and malignant tumors

• 50 AD -- Romans found that some tumors could be removed

by surgery, which would turn out to be the mainstay of

treatment for the next several hundred years

• 1939-45 -- during World War II the US Army discovered that

nitrogen mustard was effective in treating lymphoma, which

ushered in the “era of chemotherapy”

In thinking about the history of cancer, it’s --- we often get questions about, has cancer been a disease that has existed for a longtime or is it something relatively recent that has developed? It turns out that there is evidence in fossils of dinosaurs of bone cancers that appeared 70 to 80 million years ago. So cancer has been around for a long time. And then from 3000 B.C., there is evidence of cancer in mummies that were found in tombs in Egypt, and so clearly it did affect human population that was there. Around 400 B.C., we know the Greek physician, Hippocrates, was really the first physician to recognize the difference between benign and malignant tumors. And then at about 50 A.D., the Romans really first found that some of these tumors could be removed by surgery and that really turned out to be the mainstay of our treatment for the next several 100 years. It was not really until the beginning of World War II, and this was from research that was conducted by the US Army and the military, they discovered that nitrogen mustard was effective in treating some patients with lymphoma. And this really ushered in the concept of chemotherapy and the whole idea that we could use chemotherapy to treat cancer.

Ao pensarmos na história do câncer --- frequentemente, nos perguntam se o câncer é uma doença que existe há muito tempo ou que se desenvolveu recentemente. Há evidências de câncer ósseo em fósseis de dinossauros de 70 a 80 milhões de anos. Portanto, o câncer existe há muito tempo. E depois, em 3000 a.C., há evidência de câncer em múmias encontradas em tumbas no Egito; claramente, a doença afetou a população humana que habitava a região. Por volta de 400 a.C., sabemos que Hipócrates, médico grego, foi na verdade o primeiro médico a reconhecer a diferença entre tumores benignos e malignos. E depois, por volta de 50 d.C., os romanos realmente descobriram que alguns destes tumores podiam ser removidos com cirurgia; isto passou a ser a base do tratamento nos séculos seguintes. Apenas após o início da 2ª Guerra Mundial, e com pesquisa pelo Exército e as Forças Armadas dos Estados Unidos, descobriu-se que a mostarda nitrogenada era eficaz para o tratamento de alguns pacientes portadores de linfoma. Na verdade, isto foi o fato introdutor do conceito de quimioterapia e toda a ideia de que seria possível usar quimioterapia para o tratamento de câncer.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

Examples of Progress in the 20Examples of Progress in the 20Examples of Progress in the 20Examples of Progress in the 20thththth CenturyCenturyCenturyCentury

Heart DiseaseHeart DiseaseHeart DiseaseHeart Disease

500

400

300

200

100

50 55 60 65 70 75 80 85 90 95 00

De

ath

s p

er

10

0,0

00

Year

~ 514,000 Actual Deaths in 2000

~ 1,329,000 Projected Deaths

in 2000

An investment in research prevented 815,000 deaths due to coronary heart disease!!

Zerhouni, NIH 2006

One of the lessons that we’ve have learned from cardiovascular disease is that a real investment in research can lead to an impact on outcomes and improvement in life expectancy. In this slide, we are looking at the deaths per 100,000 as a --- on the Y-axis plotted against the year of the incidence of disease. So, for several years from 1950 until 1970, this was pretty consistent in terms of the projected deaths. And then due to some breakthroughs in biomedical research, we discovered that cholesterol --- the level of cholesterol in the blood, certain lifestyle, and behavioral activities were important in reducing risk for cardiovascular disease, and several medicines were discovered that you can take to lower your levels of cholesterol and other aspects that increase risk for heart disease. This led to a dramatic decrease in the number of deaths from this disease. Up until, here is 2000, but it still continued to decline. And because of this research that led to this better understanding of cardiovascular disease, you can see that we have saved over half a million people from dying from cardiovascular disease. I think this same kind of goal is achievable in cancer. Cancer is a much more complex disease than cardiovascular disease. There are many different aspects of the genetics and molecular defects that occur to cause cancer, so I think it is going to take us a little bit more research to understand exactly how we can treat it better.

Uma das lições que aprendemos com a doença cardiovascular é que um investimento real em pesquisa pode afetar os resultados e melhorar a expectativa de vida. Neste slide, examinamos os óbitos por 100.000 como um --- o eixo Y traçado em relação a um ano de incidência da doença. Portanto, durante vários anos, de 1950 até 1970, foi bem uniforme em termos de óbitos previstos. E então, graças a alguns avanços em pesquisa biomédica, descobrimos que o colesterol --- o nível de colesterol no sangue, certos estilos de vida e atividades comportamentais eram importantes na redução do risco de doença cardiovascular, e foram descobertos vários medicamentos que se podem tomar para reduzir os níveis de colesterol e outros aspectos que aumentam o risco de doença cardíaca. Isto levou a uma queda drástica no número de mortes causadas pela doença. Até então, aqui em 2000, mas a queda continua. E graças a isto, a pesquisa levou a uma melhor compreensão da doença cardiovascular, e podemos perceber que salvamos mais de meio milhão de pessoas de morrer de doença cardiovascular. Acredito que é possível alcançar este mesmo tipo de meta no câncer. O câncer é uma doença muito mais complexa do que a doença cardiovascular. Há vários aspectos diferentes de defeitos genéticos e moleculares que ocorrem e causam câncer, assim, penso que é preciso um pouco mais de pesquisa para compreender exatamente como tratá-lo melhor.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

Death Rates from Heart Disease & CancerDeath Rates from Heart Disease & CancerDeath Rates from Heart Disease & CancerDeath Rates from Heart Disease & Cancer

SEER Data

Heart Disease

Cancer

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320

Year

De

ath

s

per

10

0,0

00

75 79 83 87 91 95 99

Now looking at deaths from heart disease and cancer, you can see, heart disease deaths have gone down very dramatically, and are dipping below what we see for deaths from cancer in this slide. The heart disease is in the brown line and the ones from cancer are in the blue line. And we are at about the same point in 1999 and cardiovascular disease deaths are continuing to decrease, and those for cancer have pretty much stayed flat. They are declining somewhat, but it is a very, very small inflection compared to what we see for heart disease. So, I think with the advent of our research that we are doing now and the understanding of better molecular targets for treatment, there is a great opportunity to have the same effect that we saw in heart disease, once we understand the basis of the disease and better treatments are developed based on those molecular changes.

Agora, examinando as mortes por doença cardíaca e câncer, você pode ver que as mortes por doença cardíaca caíram drasticamente e estão bem abaixo do que vemos para mortes por câncer neste slide. A doença cardíaca é a linha marrom e a azul representa mortes por câncer. E estamos praticamente no mesmo ponto em 1999 e as mortes por doenças cardiovasculares continuam a diminuir e as causadas por câncer continuam bem constantes. De algum modo há redução, mas é uma curva muito pequena comparada com a que vemos para a doença cardiovascular. Portanto, acredito que com o advento do que nossa pesquisa está realizando e com a compreensão de melhores alvos moleculares para tratamento, há uma excelente oportunidade para ter o mesmo efeito que vimos na doença cardíaca depois de compreendermos a base da doença e os melhores tratamentos serem desenvolvidos com base nestas alterações moleculares.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

Examples of Progress in the 20Examples of Progress in the 20Examples of Progress in the 20Examples of Progress in the 20thththth Century HIV/AIDsCentury HIV/AIDsCentury HIV/AIDsCentury HIV/AIDs

Zerhouni, NIH 2006

0

10

20

30

40

50

60

70

80

90

82 84 86 88 90 92 94 96 98 00

Year

Incidence

Deaths

Nu

mb

er

of

Cas

es/D

eath

s(T

ho

us

an

ds)

1993 definitionimplementation

An investment in research reduced the death rate and disease caused by HIV/AIDs in the U.S.!!

We often get questions about how --- what is the importance of research in the development of treatments for disease, such as cancer and other treatments. I think the story that we found in the 20th century for HIV AIDS is a really good example of how biomedical research can have a dramatic impact on a disease. We are not exactly where we need to be with this disease, but clearly we have made some important advancements. And if you look at this graph, you can see the number of cases and deaths, in thousands, for the disease. And this is a disease that emerged on the population at a relatively rapid pace, starting in the early 80’s and peaking in 1992 and then going down quite dramatically after that. If you look at the peak there where the red line is, you can see that, that’s the point in time where we really understood and isolated the virus, understood what it was doing to the immune system. And that led directly to the development of drugs, which targeted the replication of the virus that were used in humans that dramatically improved the

Sempre nos perguntam sobre como --- qual é a importância da pesquisa no desenvolvimento de tratamentos para doenças como câncer e outros tratamentos. Acredito que a história que descobrimos no século XX para HIV/AIDS é realmente um bom exemplo de como a pesquisa biomédica pode ter um impacto expressivo em uma doença. Ainda não chegamos lá com relação a esta doença, mas claramente passamos por avanços importantes. Se você examinar este gráfico, verá o número de casos e óbitos, em milhares, para a doença. E esta é uma doença que surgiu na população a um ritmo relativamente rápido, começando no início da década de 1980, com pico em 1992 e, em seguida, diminuiu substancialmente. Se você examinar o pico onde se encontra a linha vermelha, verá que foi neste momento que compreendemos e isolamos o vírus, compreendemos o que ele estava provocando no sistema imunológico. E isto levou diretamente ao desenvolvimento de medicamentos, cujo alvo era a replicação do vírus, que

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outcome of these patients. And these drugs are continuingly being used today, and new drugs, second and third generations drugs are been developed, as we speak, that also targets this virus and have improved the survival of patients that have been infected with HIV. So, this is a wonderful example of how we can improve the clinical treatment when we know the molecular cause of the disease, what to target, and how to target it. We can dramatically improve the outcome, and I think it is example for what we can do in cancer once we have a better understanding of all the molecular causes of the disease.

foram usados em seres humanos, melhorando radicalmente os resultados para estes pacientes. E estes medicamentos ainda são usados hoje e novos medicamentos de segunda e terceira geração estão sendo desenvolvidos neste momento, que também têm como alvo o vírus e que melhoraram a sobrevida dos pacientes infectados pelo HIV. Portanto, este é um ótimo exemplo de como podemos melhorar o tratamento clínico quando conhecemos a causa molecular da doença, a que visar e como visar. Podemos melhorar o resultado de maneira drástica e penso que isto é um exemplo do que podemos fazer no câncer depois de compreendermos melhor todas as causas moleculares da doença.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

History of PreventionHistory of PreventionHistory of PreventionHistory of Prevention

• Recognition of carcinogenesis

• Identification of environmental exposures

The other aspect of history of cancer is the idea of prevention. And I think once we recognized some trends in cancer over the past several decades and identified some environmental exposures, we are able to recommend practices for the population to take to avoid those exposures and reduce their risk.

O outro aspecto da história do câncer á a ideia de prevenção. E eu penso que, depois de reconhecermos algumas tendências em câncer nas últimas décadas e identificarmos algumas exposições ambientais, poderemos recomendar práticas à população para evitar estas exposições e reduzir o risco.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

History of DiagnosisHistory of DiagnosisHistory of DiagnosisHistory of Diagnosis

• No early detection

• Typically presenting with large, advanced tumors

• Limited diagnostic testing available

• Cause of death often not known

Obviously, people who have exposures to environmental carcinogens are going to be higher at risk for disease. The history of diagnosis, just a little more than 30 years ago, there was really no early detection. Most of the patients typically presented with very large advanced tumors, at which time there was really not much that the physician could do in terms of treating these individuals. There was very limited diagnostic testing available. And often times the patients died without the precise cause of death being known, even though it was likely to be due to advanced cancer.

Obviamente, as pessoas que têm exposição a carcinógenos ambientais estão em situação de maior risco para a doença. Na história de diagnóstico, há pouco mais de 30 anos, não havia realmente detecção precoce. A maioria dos pacientes geralmente apresentavam grandes tumores avançados, e realmente o médico não tinha muito o que fazer para tratar destes indivíduos. Não havia muitos exames de diagnóstico disponíveis. E, frequentemente, os pacientes morriam sem que se soubesse a causa exata da doença, mesmo que, provavelmente, fosse devido a câncer avançado.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

History of TreatmentHistory of TreatmentHistory of TreatmentHistory of Treatment

• Surgery is the primary option for treatment

• 1905 x-rays used to treat skin cancers

• 1939-1945 US Army discovers that nitrogen

mustard effective in treatment of lymphoma

• 1951 first use of 6-mercaptopurine to

treat leukemia

• Limited survival for most patients

And just like I mentioned earlier, surgery is the primary option for treatment since the Romans used this a long time ago. In the early 1900’s, the x-rays were used to treat skin cancers. From 1939 to 1945, as I mentioned, the military developed this nitrogen mustard that was shown to be effective for treatment of lymphoma. Obviously, we are not using that treatment today because of the other problems, but it led to the development of a whole bunch of other types of chemotherapeutic drugs that we now have. The 6-MP was first used for treatment of leukemia in 1951. And even with those there was limited survival for most patients that presented with advanced disease.

E como eu disse anteriormente, a cirurgia era a opção primária para tratamento desde que os romanos a usaram muitos séculos antes. No início do século XX, os raios X eram usados para tratar câncer de pele. De 1939 a 1945, como eu disse, as Forças Armadas desenvolveram a mostarda nitrogenada que se mostrou eficaz para o tratamento de linfoma. Obviamente, hoje não usamos este tratamento devido a outros problemas, mas ele levou ao desenvolvimento de todo um grupo dos outros tipos de quimioterápicos que conhecemos agora. O 6-MP foi usado pela primeira para tratamento de leucemia em 1951. E mesmo com eles, as chances de sobrevida eram limitadas para a maioria dos pacientes que apresentavam doença avançada.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

Current State of PreventionCurrent State of PreventionCurrent State of PreventionCurrent State of Prevention

• Risk assessment and reduction strategies

• Tobacco cessation programs and avoidance

of other carcinogens

• Immunization hepatitis B and HPV

• Genetic counseling and limited testing

• Limited prophylactic surgery

The current state of prevention is that we have developed some very sophisticated risk assessment and reduction strategies. We know that one of the major causes of cancer is the use of tobacco, either the --- through smoking tobacco or the smokeless tobacco, and we have implemented very effective tobacco cessation programs, and we know how to counsel our patients to avoid other carcinogens in the environment. A good example of a true success in preventing liver cancer is the immunization program for hepatitis B. We know that individuals who live in an area that is endemic for hepatitis B have a very, very high incidence of hepatocellular carcinoma and that when we immunize that population for that virus, the incidence of liver cancer goes down very dramatically. The same is true for HPV and cervical cancer. A very effective vaccine has been developed that is being given to younger women and that reduces the risk of cervical cancer quite dramatically. Now, there are some patients who have a family history of cancer that is because of genetic inherited mutation in that family. And now we can map those and determine where those mutations are pretty easily, and have the family undergo genetic counseling and proper screening procedures so that we can either avoid them developing cancer or detect it early when it is much more amenable to surgery and other curative treatments. In those patients, we can do limited prophylactic surgery, which has shown to be effective, especially for some patients with hereditary forms of colon cancer and breast cancer.

O estado presente de prevenção é que criamos estratégias de avaliação e redução de risco muito sofisticadas. Sabemos que uma das maiores causas de câncer é o uso de tabaco, seja.... por fumar tabaco ou usar tabaco sem fumaça, e implementamos programas muito eficazes para cessar o uso de tabaco e sabemos como recomendar a nossos pacientes evitar outros cancerígenos no meio ambiente. Um bom exemplo de sucesso real na prevenção de câncer hepático é o programa de imunização contra hepatite B. Sabemos que nos indivíduos que moram em áreas onde a hepatite B é endêmica há incidência muito alta de carcinoma hepatocelular e quando imunizamos a população contra este vírus, a incidência de câncer hepático diminui drasticamente. O mesmo se aplica ao HPV e câncer cervical. Foi desenvolvida uma vacina muito eficaz que está sendo aplicada em mulheres jovens e que reduz substancialmente o risco de câncer cervical. Agora, há alguns pacientes que têm histórico familiar de câncer, ou seja, devido à mutação genética hereditária naquela família. Agora podemos mapear e determinar estas mutações de maneira bem fácil e fazer com que a família passe por aconselhamento genético e procedimentos de triagem apropriados de modo que possamos evitar o aparecimento do câncer ou detectá-lo em estágio inicial quando é muito mais tratável com cirurgia e outros tratamentos curativos. Em tais pacientes, podemos realizar cirurgia profilática limitada, que se mostrou eficaz, principalmente para pacientes com formas hereditárias de câncer do cólon e câncer da mama.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

Current State of DiagnosisCurrent State of DiagnosisCurrent State of DiagnosisCurrent State of Diagnosis

• Screening tests available for several

common malignancies to diagnosis

while patient asymptomatic

• Advances in imaging including improved

radiographs, CT scan and MRI

• Interventional radiology allowing for

safer biopsies

Currently, for the diagnosis of cancer, several screening tests are available for most of the common malignancies. The idea here is to diagnose the patient when they are asymptomatic. There are significant improvements in imaging, radiographs, CT scans, MRI, PET CT, and other modalities that are being developed, which are molecularly based scanning methods, look very promising. And then interventional radiology allows us to get biopsies at earlier stages and it is a much safer procedure in most cases than doing a full blown operation to do the biopsy.

Atualmente, há vários testes de triagem disponíveis para o diagnóstico do câncer para os tipos mais comuns de processos malignos. A ideia aqui é o diagnóstico do paciente quando forem assintomáticos. Há melhorias significativas em diagnóstico por imagem, radiografias, tomografias, RM, PET e outras modalidades que estão sendo desenvolvidas, que são métodos moleculares de varredura, que parecem promissores. A radiologia intervencionista nos permite obter biópsias em estágios precoces e é um procedimento muito mais seguro na maioria dos casos do que fazer uma cirurgia completa para obter a biópsia.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

Current State of TreatmentCurrent State of TreatmentCurrent State of TreatmentCurrent State of Treatment

• Multidisciplinary care with advances in surgery, radiation therapy and drug treatment

• Surgery typically required for cure of solid tumors

• Chemotherapy and radiation therapy given to improve the likelihood of cure or for palliation of patients with non-curable disease

• Radiation therapy advances in improvement in safety with Intensity Modulated Radiation Therapy (IMRT) and protons

• Expanding use of targeted therapies, usually in addition to chemotherapy

The idea of treatment --- the approach to treatment has really tremendously evolved since the World War II era. And now in most of the modern larger cancer centers, in the country, use a multidisciplinary care approach that brings the surgeons, the radiation therapist, and the oncologist --- the medical oncologist all together in one venue to really use their brain power and the best treatment for the patient for the stage and diagnosis of tumor that they have. For early lesions of the GI tract and others, we can cure those with surgery. There are clearly certain tumors where a combination of chemotherapy and radiation therapy improves the likelihood for cure, especially, for example, in rectal cancer and some others. And then radiation therapy has advanced, and the IMRT has really improved the --- how they can focus the therapy. And also with the advent of proton therapy that makes it a lot more targeted. And then lastly, through the development of more modern technologies to detect molecular defects in cancers, there has been a parallel development in targeted therapies. And so that if we can match that targeted therapy with the molecular defects of

A ideia de tratamento --- a abordagem ao tratamento teve evolução extraordinária desde a 2ª Guerra Mundial. E agora, na maioria dos centros de tratamento de câncer modernos e maiores, no país, usam uma abordagem multidisciplinar de cuidados que reúne cirurgiões, radioterapeutas e o oncologista --- o oncologista médico, todos juntos em um único lugar para realmente usar sua capacidade mental e o melhor tratamento para o paciente para o estágio e diagnóstico do seu tumor. Para lesões precoces do trato GI e outros, a cura é por cirurgia. Claramente, há certos tumores em que a combinação de quimioterapia e radioterapia melhora a probabilidade de cura, principalmente, por exemplo, câncer retal e alguns outros. A radioterapia progrediu e a IMRT realmente melhorou --- como se focam em terapia. E também com o advento da terapia por próton, que a torna mais direcionada. E finalmente, através do desenvolvimento de tecnologias mais modernas para detectar defeitos moleculares em câncer, ocorreu um desenvolvimento paralelo em terapias direcionadas. E então se pudermos combinar aquela terapia direcionada com os defeitos

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an individual’s tumor, we already know that the treatment outcome is going to be much better when the therapy is matched to the tumor. So, there is a lot of effort underway in most all of the cancers centers to determine which molecular endpoints need to be measured and which therapies need to be given to those individualized patients.

moleculares do tumor de um indivíduo, já sabemos que o resultado do tratamento será muito melhor quando a terapia for compatível com o tumor. Portanto, há muito esforço sendo realizado na maioria dos centros para tratamento de câncer para determinar quais critérios de avaliação devem ser medidos e quais terapias precisam ser administradas a cada paciente.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

Future of PreventionFuture of PreventionFuture of PreventionFuture of Prevention

• More extensive genetic testing

• Avoidance of carcinogens (tobacco, sun, etc.)

• Chemoprevention

• More prophylactic surgery

• Better diet

• Regular exercise routine

• Stress reduction

In the future of prevention with the improvements in DNA sequencing technology and other detection technologies, I think we are going to have a lot more extensive use of this and know --- and be able to predict ahead of time who is at the highest risk for cancer and intervene even before the cancer cells start growing in individual patients. Clearly, avoidance of carcinogens should be the mainstay for cancers that develop as a result of tobacco, sun exposure, and other environmental carcinogens. If we could completely abolish smoking in our population, we could probably reduce the incidence of cancer by over 50%. So, this would have a very dramatic impact not only on people’s survival, but also the high cost of heathcare. Chemoprevention is an area that has developed in terms of people taking certain drugs or preventatives that they can reduce their risk for cancer. A good example of this is that people who take aspirin have about a 40% to 50% reduction in their risk for colorectal cancer and some other cancers as well. I think more targeted use of prophylactic surgery, especially in those patients who undergo molecular diagnosis can be useful. We can always improve our diet, exercise, and stress reduction. And we know that if we do something on those fronts, that it dramatically reduces our risk for cancer, as well as cardiovascular and other diseases.

No futuro da prevenção com as melhorias na tecnologia de sequenciamento de DNA e outras tecnologias de detecção, acredito que teremos um uso mais amplo disto e saber --- e poder prever quem está em maior risco de câncer e intervir mesmo antes que as células cancerígenas comecem a crescer nos pacientes. Claramente, evitar carcinógenos deve ser a base para os tipos de câncer que ocorrem como resultado do uso de tabaco, exposição ao sol e outros carcinógenos ambientais. Se pudéssemos abolir por completo o fumo na população, provavelmente teríamos uma redução na incidência de câncer de mais de 50%. Portanto, isto teria um impacto drástico não apenas na sobrevida das pessoas como também no alto custo dos cuidados de saúde. A quimioprevenção é uma área que evoluiu em termos de pessoas que tomam determinados medicamentos ou preventivos que podem reduzir seu risco de câncer. Por exemplo, se o indivíduo toma aspirina, ele tem cerca de 40% a 50% de redução no risco de ter câncer colorretal bem como outros tipos de câncer. Acredito que o uso mais direcionado da cirurgia profilática, especialmente em pacientes que passam por diagnóstico molecular, pode ser útil. Sempre podemos melhorar nossa dieta, fazer exercício e reduzir o estresse. E sabemos que se agirmos nestas frentes, há uma redução drástica de nosso risco para o câncer, bem como doenças cardiovasculares e outras.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

Future of DiagnosisFuture of DiagnosisFuture of DiagnosisFuture of Diagnosis

• Improved early diagnoses with enhanced screening

• Better biomarkers for early disease

• Screening options for diseases not currently available

• Screening based on genetic risk

• Blood tests to identify tumor markers, malignant cells, and genetic markers

For the future of diagnosis, again there are going to be a lot of improvements in our ability to image and diagnosis early. We are already developing better biomarkers for early disease. These are things that can be measured in the blood, or other --- urine, or other bodily fluids that are a beacon for the presence of an early cancer that tells the physician we need to look into this more carefully and intervene when that is needed. We are developing screening options for other diseases that currently are unavailable. And also we need to do more intense screening for those that have a high genetic risk and continue to develop these blood tests and other early markers for this screening cancer.

Quanto ao futuro do diagnóstico, novamente, temos muito a melhorar em nossa capacidade para realizar exames por imagem e diagnóstico precoce. Estamos já desenvolvendo melhores biomarcadores para doença em estágio inicial. Isto pode ser mensurado no sangue ou outro.... urina, ou outro líquido corporal que indique a presença precoce de câncer e que indica ao médico que precisamos examinar isto mais atentamente e intervir quando necessário. Estamos desenvolvendo opções de triagem para outras doenças que não estão atualmente disponíveis. Precisamos também fazer triagem mais intensiva para aqueles com alto risco genético e continuar a desenvolver exames de sangue e outros marcadores precoces para esta triagem de câncer.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

Future of TreatmentFuture of TreatmentFuture of TreatmentFuture of Treatment

• Development of additional novel drug treatments including molecular targets with less emphasis on cytotoxic therapy

• Gene therapy using different approaches

• Individualization of treatment plans based on cancer biology and genetic profile in “real time”

• Enhanced emphasis on quality of life and toxicities as patients on treatment for longer durations

• Higher cure rates for some patients and longer life expectancies for others with active disease

There’s --- in the future of treatment, there is a tremendous amount of drug development underway. There are thought to be 800 or 900 drugs that are being developed, as we speak, that target different pathways that go awry in the cancer tissue. And these are being tested clinically and preclinically now, and will be becoming forward over the next 5 to 10 years. Gene therapy hasn’t proven to be all that effective. There are new methods of giving gene therapy that may be better and we will have to see how that goes. I think the big improvement is going to be individualizing and personalizing the treatment plan based on the biology and molecular defects of the cancer, and doing this in real time because cancers become resistant to treatments. If we can detect those molecular changes that make the cancer resistant, right away, we can avoid treating the patients with drugs that are not going to be effective, and ensure that they get put on drugs that are going to be maximally effective. We need to still consider quality of life in our patients in reducing toxicities from some of the treatment options. And then, I think we will see higher

Há... no futuro do tratamento, há um grande número de medicamentos em desenvolvimento. Acredita-se que há 800 ou 900 medicamentos em desenvolvimento neste momento, cujo alvo são caminhos diferentes que dão errado no tecido canceroso. Eles estão passando por testes clínicos e pré-clínicos e estarão disponíveis nos próximos 5 a 10 anos. A terapia genética provou não ser tão eficaz. Há novos métodos de fornecer terapia genética que podem ser melhores e teremos que ver como funcionam. Acredito que a maior melhoria será individualizar e personalizar o plano de tratamento com base em defeitos biológicos e moleculares do câncer e fazê-lo em tempo real porque os cânceres passam a ser resistentes a tratamentos. Se pudermos detectar estas mudanças moleculares que tornam o câncer resistente, rapidamente, poderemos evitar tratar os pacientes com medicamentos que não são eficazes e faremos com que recebam medicamentos que tenham eficácia máxima. Ainda precisamos considerar a qualidade de vida em nossos pacientes ao reduzir a toxicidade de algumas opções de tratamento. Assim, eu acredito que veremos

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cure rates for some patients, but the main thing we are going to see over the next 5 to 10 to 20 years is that people with cancer are going to be able to survive a lot longer with their disease than they have in the past. And this is analogous to what we see in patients who have diabetes [and] heart disease. A lot of times, in the past, those people would have died very early in the course of their disease and with the advent of using insulin, and stenting, and cardiovascular surgeries, those people survive much longer. We are going to see the same thing in cancer because we are going to be able to target the specific problems in those cancer cells. We may not be able to kill all of the cancer cells immediately, but we will prolong the lives of these people quite dramatically. And in some patients we will improve the cure rates

índices de cura mais altos para alguns pacientes, mas o que mais veremos nos próximos 5, 10 ou 20 anos é que portadores de câncer poderão viver muito mais com sua doença do que no passado. Isto é comparável a o que vemos em pacientes portadores de diabete [e] doença cardíaca. No passado, muitas vezes, aquelas pessoas teriam morrido precocemente no curso da doença e com o advento do uso de insulina e stents e cirurgias cardiovasculares elas sobrevivem por muito mais tempo. Veremos algo semelhante com o câncer porque poderemos visar a problemas específicos naquelas células cancerosas. Provavelmente não poderemos matar todas as células cancerosas, mas prolongaremos a vida destas pessoas de maneira drástica. E em alguns pacientes, melhoraremos os índices de cura.

History of CancerHistory of CancerHistory of CancerHistory of Cancer

Our Best Hope for the Future: Our Best Hope for the Future: Our Best Hope for the Future: Our Best Hope for the Future:

Transform Medicine Through DiscoveryTransform Medicine Through DiscoveryTransform Medicine Through DiscoveryTransform Medicine Through Discovery

Predictive

Personalized

PreemptiveZerhouni, NIH 2006Zerhouni, NIH 2006

So, just to summarize some of thoughts that I have discussed with you over this short lecture, I think, first of all, we are going to improve the outcome by being more predictive of who gets disease, when we need to intervene, and how to prevent that from happening. We need to personalize the treatment to the tumor and to the individual patient. We are getting better at doing that, and that is going to continue to develop at a accelerated pace over the next 5 to 10 years, and there are going to be some tremendous opportunities there. And then lastly, being preemptive and doing something before it is too late is going to lead to a much, much better outcome. And all of this is going to be made possible because of the research that is underway that is giving us new knowledge, a better understanding of the disease, and pointing us in the direction for how we can impact our ability to predict, personalize, and preempt patients with cancer.

Assim, resumindo algumas ideias que discuti com vocês nesta breve aula, penso que, em primeiro lugar, melhoraremos o resultado prevendo melhor quem adoece, quando precisamos intervir e como evitar que isso aconteça. Precisamos personalizar o tratamento do tumor e para cada paciente. Nosso desempenho neste caso melhorou e ele continuará a se desenvolver em um ritmo acelerado nos próximos 5 a 10 anos quando haverá oportunidades excelentes. E finalmente, a prevenção e ação antes que seja tarde demais levarão a resultados muito melhores. Tudo isto será possível porque há pesquisas em andamento que nos dão um melhor conhecimento e melhor compreensão da doença, indicando a direção de como podemos afetar nossa capacidade de prever, personalizar e antecipar pacientes com câncer.

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History of CancerHistory of CancerHistory of CancerHistory of Cancer

ConclusionsConclusionsConclusionsConclusions

• Cancer affects approximately 40% of the

US population

• Although there have been gradual increases in

survival following a cancer diagnosis, cancer is

the leading cause of death for those under the

age of 85

• Advances in cancer prevention, diagnosis and

treatment are anticipated in the future with

personalized patient care

So, just to conclude the discussion here, cancer is going to affect 40% of the U.S. population. The incidence is going to be continuing to increase based on the age of the population. We have an aging population in the U.S. and Western Europe, and I think that we are just going to see more disease, as we go forward. There have been gradual increases in survival in patients following a cancer diagnosis. But it is the leading cause of death in those under age of 85, and it will exceed the death rates from cardiovascular disease in the next 5 to 10 years. Advances in cancer prevention, diagnosis, and treatment will make a huge impact, and I think we are going to see, as we go forward, this idea of personalizing cancer therapy, matching the treatment, not only the chemotherapy or personalized therapy, but also radiation therapy and the surgery. And personalizing that treatment for the individual patient is going to dramatically improve the outcomes. And I am very optimistic that we will continue to see the survival time for our patients increase. So, that concludes my discussion on the history of cancer and the importance of research, and I really want to thank you for listening today.

Para concluir esta discussão, o câncer afetará 40% da população norte-americana. A incidência continuará a aumentar com base na idade da população. Nos Estados Unidos e Europa ocidental enfrentamos o envelhecimento populacional e acredito que veremos mais doenças no correr dos anos. Houve aumentos graduais na sobrevida de pacientes após o diagnóstico de câncer. Mas este é a principal causa de óbito em pessoas abaixo de 85 anos e superará os índices de mortalidade por doença cardiovascular nos próximos 5 a 10 anos. Avanços na prevenção, diagnóstico e tratamento de câncer terão grande impacto e penso que veremos, ao avançarmos, esta ideia de terapia personalizada contra o câncer, combinando o tratamento, não apenas quimioterapia ou terapia personalizada mas também radioterapia e cirurgia. E a personalização do tratamento de cada paciente melhorará drasticamente os resultados. Estou muito otimista de que continuaremos a ver o aumento do tempo de sobrevida em nossos pacientes. Portanto, isso conclui nossa discussão sobre a história do câncer e a importância da pesquisa e quero agradecer a vocês por sua participação.