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History of Cancer

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Historia del cáncer

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Professional Oncology Education

History of Cancer

Time: 21:28

Educación Oncológica Profesional

Historia del cáncer

Duración: 21:28

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

Provost & Executive Vice President

The University of Texas, MD Anderson Cancer Center

Dr. Raymond DuBois

Vicerrector y Vicepresidente Ejecutivo

Universidad de 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.

Hola. Soy Ray DuBois, Vicerrector y Vicepresidente

Ejecutivo del MD Anderson Cancer Center de la

Universidad de Texas. Hoy hablaré de la historia del

cáncer, cómo ha evolucionado esta enfermedad a lo largo

de cientos de años y qué sabemos de ella. Además,

veremos el importante papel de las futuras

investigaciones, cómo desarrollar nuevas terapias, y otros

aspectos del tratamiento y la prevención del cáncer.

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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.

Este análisis nos dará una mejor apreciación del alcance

de este problema en la población estadounidense.

Explicaré cómo las grandes inversiones en investigación

pueden afectar la enfermedad, y cuáles son las tendencias

inminentes en prevención, diagnóstico y tratamiento del

cáncer.


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.

Al observar la incidencia del cáncer en los Estados

Unidos, estimamos que en 2009 se diagnosticaron cerca

de 1.5 millones de nuevos casos, que equivale a un riesgo

de por vida del 40%. En general, hubo un leve descenso

del 1.1% entre 1999 y 2006, principalmente por una

menor incidencia y mortalidad del cáncer de colon y

mama, que en las mujeres se ha estabilizado hasta cierto

punto. La tasa de supervivencia a cinco años fue del 66%

entre 1999 y 2005. En las tasas de mortalidad hay un

riesgo de por vida del 21% —una importante causa de

muerte por cáncer en personas menores de 85 años—,

pero hay una disminución en la mortalidad. Ha sido leve,

pero consistente, especialmente en el cáncer de pulmón,

mama y colon.

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• 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.

En cuanto a la historia del cáncer, a veces nos preguntan

si ha existido durante un largo tiempo o si se ha

desarrollado recientemente. Hay evidencia de fósiles de

dinosaurios con cáncer de hueso de hace 70 a 80 millones

de años. El cáncer ha existido durante mucho tiempo.

Hay evidencias de cáncer en momias de tumbas egipcias

del año 3000 a.C. Claramente, la enfermedad afectaba a

la población humana. Alrededor del año 400 a.C., el

médico griego Hipócrates fue el primero en reconocer la

diferencia entre tumores benignos y malignos. Más

adelante, cerca del año 50 d.C., los romanos fueron los

primeros en descubrir que algunos tumores podían ser

removidos quirúrgicamente, lo cual fue la base del

tratamiento por cientos de años. Recién a comienzos de la

Segunda Guerra Mundial, gracias a una investigación del

Ejército de los Estados Unidos, descubrimos que la

mostaza nitrogenada era eficaz para tratar algunos

pacientes con linfoma. Esto fue lo que introdujo el

concepto de quimioterapia y la idea de utilizarla para

tratar el cáncer.

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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.

Una de las lecciones aprendidas de la enfermedad

cardiovascular es que una inversión adecuada en

investigación puede tener un impacto en los resultados y

mejorar la esperanza de vida. En esta diapositiva vemos

en el eje vertical la cantidad de muertes, en centenas de

miles, graficadas en función del año de incidencia de la

enfermedad. Durante varios años —desde 1950 hasta

1970—, las cifras eran consistentes en términos de

muertes previstas. Luego, gracias a los avances en la

investigación biomédica, descubrimos que el nivel de

colesterol en la sangre, determinados estilos de vida y las

actividades conductuales eran importantes para reducir el

riesgo de enfermedad cardiovascular. Asimismo, se

descubrieron numerosos medicamentos para reducir los

niveles de colesterol y otros factores que aumentan el

riesgo de enfermedad cardíaca. Esto condujo a una

disminución radical en la cantidad de muertes provocadas

por esta enfermedad. Aquí vemos los valores hasta el año

2000, pero siguieron disminuyendo. Esta investigación

permitió una mejor comprensión de la enfermedad

cardiovascular y hemos evitado que más de medio millón

de personas fallecieran por esta causa. Esa misma meta se

puede alcanzar con el cáncer, aunque es una enfermedad

mucho más compleja que la enfermedad cardiovascular.

Son muchos los defectos genéticos y moleculares que

causan cáncer, y debemos seguir investigando para

entender exactamente cómo tratarlo mejor.

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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

240

220

200

180

160

260

280

300

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.

Si consideramos las muertes por cáncer y enfermedad

cardíaca, estas últimas han disminuido drásticamente y

son cada vez menores en relación con las muertes por

cáncer. La línea marrón representa las muertes por

enfermedad cardíaca y la línea azul, las muertes por

cáncer. En 1999 alcanzan el mismo punto, pero las

muertes por enfermedad cardiovascular continúan

decreciendo, en tanto que las de cáncer han permanecido

relativamente estables. Se han reducido un poco, pero es

una inflexión muy pequeña comparada con la enfermedad

cardíaca. Creo que con las investigaciones actuales y una

mejor comprensión de los objetivos moleculares para el

tratamiento hay una gran oportunidad para lograr el

mismo efecto que en la enfermedad cardíaca una vez que

comprendamos la base de la enfermedad y se desarrollen

mejores tratamientos basados en esos cambios

moleculares.


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

outcome of these patients. And these drugs are

A menudo nos preguntan cuál es la importancia de la

investigación en el desarrollo de tratamientos para

enfermedades como el cáncer. La historia del VIH y el

sida durante el siglo XX es un buen ejemplo de cómo la

investigación biomédica puede tener gran impacto en una

enfermedad. Aún no la hemos vencido, pero son

evidentes ciertos avances importantes. Esta gráfica

muestra el número de casos y muertes en miles. Es una

enfermedad que surgió en la población a un ritmo

relativamente rápido: comenzó a principios de la década

de los ochenta, alcanzó su pico en 1992, y luego comenzó

a descender de manera bastante drástica. El pico,

marcado con la línea roja, es el punto en el tiempo

cuando comprendimos y aislamos el virus, y cuando

entendimos cómo actuaba sobre el sistema inmunológico.

Esto condujo directamente al desarrollo de medicamentos

dirigidos a su replicación, que fueron utilizados en seres

humanos y mejoraron notablemente los resultados en los

pacientes. Hoy en día se emplean continuamente, pero se

están desarrollando nuevos medicamentos —de segunda

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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.

y tercera generación— dirigidos al virus, que también

aumentan la supervivencia de los pacientes infectados

con VIH. Por lo tanto, este es un maravilloso ejemplo de

cómo podemos mejorar el tratamiento clínico cuando se

conoce la causa molecular de la enfermedad, cuál es el

objetivo y cómo atacarlo. Podemos mejorar radicalmente

los resultados, y es un ejemplo de qué puede lograrse con

el cáncer una vez que comprendamos mejor todas sus

causas moleculares.


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.

Otro aspecto de la historia del cáncer es la idea de la

prevención. Una vez que reconocimos algunas tendencias

del cáncer en las últimas décadas e identificamos ciertas

exposiciones ambientales, pudimos recomendar a la

población reglas prácticas para evitar esas exposiciones y

reducir el riesgo.

7


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, las personas expuestas a los carcinógenos

ambientales tienen un mayor riesgo de desarrollar la

enfermedad. La historia del diagnóstico comenzó hace

poco más de 30 años, cuando aún no había una detección

temprana. La mayoría de los pacientes presentaban

tumores avanzados y de gran tamaño. En esa etapa, el

médico poco podía hacer en términos de tratamiento. Los

exámenes de diagnóstico eran muy limitados, y muchas

veces los pacientes morían sin que se conociera la causa

exacta, a pesar de que era probable que se debiera a un

cáncer avanzado.


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.

Ya mencionamos que los romanos utilizaban la cirugía

hace mucho tiempo y que desde entonces fue la principal

opción de tratamiento. A comienzos del siglo XX se

utilizaban los rayos X para tratar el cáncer de piel. De

1939 a 1945, los militares desarrollaron la mostaza

nitrogenada, que demostró eficacia para tratar el linfoma.

Ya no la utilizamos debido a sus efectos secundarios,

pero condujo al desarrollo de numerosos medicamentos

quimioterapéuticos. El 6-MP se utilizó para tratar la

leucemia por primera vez en 1951; sin embargo, aun con

estos medicamentos, la supervivencia era limitada para la

mayoría de los pacientes con enfermedad avanzada.

8


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.

Actualmente, la prevención cuenta con sofisticadas

estrategias de evaluación y reducción de riesgos. Una de

las principales causas de cáncer es el tabaco, ya sea

fumado o consumido sin humo. Hemos implementado

programas antitabaco altamente eficaces y sabemos cómo

asesorar a nuestros pacientes para que eviten otros

carcinógenos ambientales. Un buen ejemplo de un

verdadero éxito en la prevención del cáncer de hígado es

el programa de vacunación contra la hepatitis B. Sabemos

que quienes viven en un área endémica con hepatitis B

tienen una incidencia muy alta de carcinoma

hepatocelular, y al vacunar a la población contra ese virus

la incidencia de cáncer de hígado disminuye

drásticamente. Lo mismo es cierto del VPH y el cáncer

cervicouterino. Se ha desarrollado una vacuna muy eficaz

para mujeres jóvenes que reduce drásticamente el riesgo

de cáncer cervicouterino. Actualmente, tenemos

pacientes con antecedentes familiares de cáncer por

mutación genética hereditaria. Ahora podemos mapearla

y determinar fácilmente dónde se encuentra. La familia

debe recibir asesoramiento genético y procedimientos de

detección adecuados que ayuden a evitar que desarrollen

cáncer, o a detectarlo de manera temprana, cuando es

mucho más susceptible a la cirugía y otros tratamientos

curativos. En estos pacientes podemos realizar una

cirugía profiláctica limitada, que ha demostrado ser

efectiva, especialmente en pacientes con formas

hereditarias de cáncer de colon y mama.

9


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.

En la actualidad, para diagnosticar cáncer, disponemos de

numerosas pruebas de diagnóstico para la mayoría de las

neoplasias comunes. La idea es diagnosticar pacientes

asintomáticos. Se han producido mejoras considerables

en diagnóstico por imágenes, radiografías, tomografías

computadas, resonancias magnéticas, tomografías PET y

otras modalidades que están siendo desarrolladas, como

los métodos de detección molecular y que parecen muy

promisorias. La radiología intervencionista permite tomar

biopsias en fases más tempranas y en la mayoría de los

casos es mucho más segura que una operación de biopsia

completa.


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

El enfoque del tratamiento ha evolucionado mucho desde

la Segunda Guerra Mundial. Ahora, la mayoría de los

centros oncológicos más grandes y modernos del país

utilizan un enfoque multidisciplinario que reúne en un

mismo sitio a cirujanos, radioterapeutas y oncólogos para

aprovechar sus capacidades y utilizar el mejor

tratamiento para el paciente según la etapa y el

diagnóstico del tumor. Las lesiones tempranas del tracto

gastrointestinal y de otro tipo pueden curarse con cirugía.

En ciertos tumores, una combinación de quimioterapia y

radioterapia mejora la probabilidad de cura; por ejemplo,

en el cáncer rectal. La radioterapia ha avanzado, y la

versión de intensidad modulada o IMRT ha mejorado el

enfoque de la terapia. Además, la terapia de protones es

mucho más específica. Por último, con el desarrollo de

tecnologías más modernas para detectar defectos

moleculares en el cáncer, se ha producido un desarrollo

paralelo de las terapias dirigidas. Si podemos

compatibilizar la terapia dirigida con los defectos

moleculares del tumor de una persona, y si el tratamiento

es compatible con el tumor, el resultado será superior. En

10

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.

la mayoría de los centros oncológicos se están realizando

actividades para determinar qué parámetros moleculares

deben medirse y qué terapias se deben administrar a cada

paciente.


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.

En cuanto al futuro de la prevención, con las mejoras en

la tecnología de secuenciación de ADN y otros métodos

de detección de uso creciente, podremos predecir quiénes

tienen mayor riesgo de padecer cáncer e intervenir

incluso antes de que las células cancerosas comiencen a

crecer en un paciente determinado. Claramente, evitar los

carcinógenos es fundamental para los cánceres que son

consecuencia del tabaco, la exposición al sol y otros

carcinógenos ambientales. Si pudiéramos eliminar por

completo el tabaquismo en nuestra población,

probablemente reduciríamos la incidencia de cáncer en

más del 50%. Esto tendría un importante impacto, no sólo

en la supervivencia de las personas, sino también en el

alto costo del cuidado de la salud. La quimioprevención,

un área de reciente desarrollo, consiste en tomar

medicamentos o preventivos para reducir el riesgo de

cáncer. Un buen ejemplo son las personas que toman

aspirina, que reducen del 40% al 50% el riesgo de cáncer

colorrectal, al igual que otros tipos de cáncer. Un uso más

dirigido de la cirugía profiláctica puede ser útil,

especialmente en pacientes con diagnóstico molecular.

Siempre podemos mejorar la dieta y ejercicio, y reducir el

estrés. Además, sabemos que esto reduce drásticamente

el riesgo de cáncer, enfermedad cardiovascular y otras

enfermedades.

11


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.

En cuanto al futuro del diagnóstico, habrá numerosas

mejoras en la capacidad de captar imágenes y realizar

diagnósticos tempranos. Ya estamos desarrollando

mejores biomarcadores para enfermedades precoces.

Pueden medirse en sangre, orina y otros fluidos

corporales, y son indicadores de cáncer precoz que llevan

al médico a estudiar la información más detenidamente e

intervenir cuando sea necesario. Para otras enfermedades,

estamos desarrollando métodos de detección que

actualmente no están disponibles. También debemos

realizar exámenes de detección más intensos en personas

con alto riesgo genético, y seguir desarrollando análisis

de sangre y otros marcadores tempranos para detectar el

cáncer.


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

En cuanto al futuro del tratamiento, estamos realizando

un importante desarrollo de medicamentos. Se estima que

actualmente se están desarrollando 800 o 900

medicamentos dirigidos a las diferentes vías alteradas por

el tejido canceroso. Están siendo probados clínica y

preclínicamente, y estarán disponibles en los próximos 5

a 10 años. La terapia genética no ha demostrado ser

totalmente eficaz. Existen nuevos métodos para

administrar terapia genética que podrían dar mejores

resultados. La gran mejora será individualizar y

personalizar un plan de tratamiento basado en la biología

y los defectos moleculares del cáncer, y hacerlo en

tiempo real, porque los cánceres adquieren resistencia a

los tratamientos. Si podemos detectar inmediatamente los

cambios moleculares que los hacen resistentes, podremos

evitar los tratamientos con medicamentos que no serán

eficaces y administrar aquellos que tendrán una máxima

eficacia. Debemos seguir teniendo en cuenta la calidad de

vida de los pacientes y reducir la toxicidad de algunas

opciones de tratamiento. Recién entonces tendremos tasas

de cura más altas para algunos pacientes, pero lo que más

12

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

veremos en los próximos 5, 10 o 20 años es que las

personas con cáncer podrán sobrevivir más tiempo con la

enfermedad que en el pasado. Esto es análogo a lo

ocurrido en pacientes con diabetes y enfermedad

cardíaca. En el pasado, muchos hubieran muerto al

comienzo de la enfermedad, pero con el advenimiento de

la insulina, los stents y la cirugía cardiovascular, ahora

sobreviven mucho más tiempo. Veremos lo mismo con el

cáncer, porque podremos atacar problemas específicos en

las células cancerosas. Es posible que no podamos matar

de inmediato todas las células cancerosas, pero

prolongaremos considerablemente la vida de los

pacientes y, en algunos casos, incluso mejoraremos las

tasas de cura.


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.

Resumamos entonces algunos de los conceptos expuestos

en esta breve disertación. En primer lugar, creo que

mejoraremos los resultados al poder predecir quién

padecerá la enfermedad, cuándo intervenir y cómo evitar

que algo suceda. Debemos personalizar el tratamiento y

adaptarlo al tumor y al paciente individual. Estamos

perfeccionando métodos que continuarán desarrollándose

a un ritmo acelerado en los próximos 5 a 10 años, lo que

nos dará excelentes oportunidades. Por último, las

prácticas preventivas y la intervención anticipada nos

conducirán a mejores resultados. Todo esto será posible

gracias a la investigación que se está llevando a cabo, la

cual nos está proporcionando nuevos conocimientos y

una mejor comprensión de la enfermedad, y que muestra

cómo mejorar nuestra capacidad de predecir, personalizar

y prevenir la enfermedad en pacientes con cáncer.

13


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 presentación, tengamos en cuenta que

el cáncer afectará al 40% de la población de los Estados

Unidos. Esta incidencia continuará aumentando con la

edad. La población de los Estados Unidos y Europa

Occidental está envejeciendo, y veremos más enfermedad

con el transcurso del tiempo. Ha habido un aumento

gradual en la supervivencia de los pacientes con

diagnóstico de cáncer; sin embargo, es la principal causa

de muerte en personas menores de 85 años, y estos

valores superarán las tasas de mortalidad por enfermedad

cardiovascular en los próximos 5 a 10 años. Los avances

en prevención, diagnóstico y tratamiento del cáncer

tendrán un impacto enorme, y podremos personalizar la

terapia y compatibilizar el tratamiento, no sólo la

quimioterapia o la terapia personalizada, sino también la

radioterapia y la cirugía. La personalización del

tratamiento para cada paciente mejorará drásticamente los

resultados. Soy muy optimista y creo que seguiremos

viendo un aumento en la sobrevida de nuestros pacientes.

Esto concluye mi análisis sobre la historia del cáncer y la

importancia de la investigación. Le agradezco su

atención.

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