{"id":113586,"date":"2012-07-10T16:35:33","date_gmt":"2012-07-10T20:35:33","guid":{"rendered":"\/gazette\/?p=113586"},"modified":"2019-03-06T15:21:05","modified_gmt":"2019-03-06T20:21:05","slug":"transforming-cancer-treatment","status":"publish","type":"post","link":"https:\/\/news.harvard.edu\/gazette\/story\/2012\/07\/transforming-cancer-treatment\/","title":{"rendered":"Transforming cancer treatment"},"content":{"rendered":"\n\t
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\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak (left), director of the Program for Evolutionary Dynamics. Nowak and his team, including Benjamin Allen (right), a postdoctoral fellow in mathematical biology, focused on a multidrug approach to treatment that could make many cancers manageable, if not curable. <\/p>

Stephanie Mitchell\/Harvard Staff Photographer<\/p><\/figcaption><\/figure>\n\n\t

\n\t\t\t\n\t\t\tHealth\t\t<\/a>\n\t\t\n\t\t

\n\t\tTransforming cancer treatment\t<\/h1>\n\n\t\n\t\t\t<\/div>\n\t\t\n\t
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\n\t\tPeter Reuell\t<\/p>\n\t\t\t

\n\t\t\tHarvard Staff Writer\t\t<\/p>\n\t\t\t\t\t<\/address>\n\t\t<\/div>\n\n\t\t

\n\t\t\tMultidrug strategy emerges from new research\t\t<\/h2>\n\t\t\n<\/header>\n\n\n\n
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A Harvard<\/a> researcher studying the evolution of drug resistance<\/a> in cancer<\/a> says that, in a few decades, \u201cmany, many cancers could be manageable.\u201d<\/p>\n

\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak, a professor of mathematics and of biology and director of the Program for Evolutionary Dynamics<\/a>. \u201cOne hundred years ago, many people died of bacterial infections. Now, we have treatment for such infections \u2014 those people don\u2019t have to die. I believe we are approaching a similar point with cancer.\u201d<\/p>\n

Nowak is one of several co-authors of a paper, published in Nature<\/a> on June 28, that details how resistance to targeted drug therapy emerges in colorectal cancers and describes a multidrug approach to treatment that could make many cancers manageable, if not curable.<\/p>\n

The key, Nowak\u2019s research suggests, is to change the way clinicians battle the disease.<\/p>\n

Physicians and researchers in recent years have increasingly turned to \u201ctargeted therapies<\/a>\u201d \u2014 drugs that combat cancer by interrupting its ability to grow and spread \u2014 rather than traditional chemotherapy<\/a>, but such treatment is far from perfect. Most targeted therapies are effective for only a few months before the cancer evolves resistance to the drugs.<\/p>\n

The culprit in the colon cancer treatment examined in the Nature paper is the KRAS gene<\/a>, which is responsible for producing a protein to regulate cell division. When activated, the gene helps cancer cells develop resistance to targeted-therapy drugs, effectively making the treatment useless.<\/p>\n

To better understand what role the KRAS gene plays in drug resistance, a team of researchers led by Bert Vogelstein, the Clayton Professor of Oncology and Pathology at the Johns Hopkins Kimmel Cancer Center, launched a study that began by testing patients to determine if the KRAS gene was activated in their tumors. Patients without an activated KRAS gene underwent a normal round of targeted therapy treatment, and the initial results \u2014 as expected \u2014 were successful. Tests performed after the treatment broke down, however, showed a surprising result: The KRAS gene had been activated.<\/p>\n

As part of the research, Vogelstein\u2019s team analyzed a handful of mutations that can lead to the activation of the KRAS gene. To help interpret those results, they turned to Nowak\u2019s team, including mathematicians Benjamin Allen, a postdoctoral fellow in mathematical biology, and Ivana Bozic<\/a>, a postdoctoral fellow in mathematics.<\/p>\n

Analyzing the clinical results, Allen and Bozic were able to mathematically describe the exponential growth of the cancer and determine whether the mutation that led to drug resistance was pre-existing, or whether it occurred after treatment began. Their model was able to predict, with surprising accuracy, the window of time from when the drug is first administered to when resistance arises and the drug begins to fail.<\/p>\n

\u201cBy looking at their results mathematically, we were able to determine conclusively that the resistance was already there, so the therapy was doomed from the start,\u201d Allen said. \u201cThat had been an unresolved question before this study. Clinicians were finding that these kinds of therapies typically don\u2019t work for longer than six months, and our finding provides an explanation for why that failure occurs.\u201d<\/p>\n

Put simply, Nowak said, the findings suggest that, of the billions of cancer cells that exist in a patient, only a tiny percentage \u2014 about one in a million \u2014 are resistant to drugs used in targeted therapy. When treatment starts, the nonresistant cells are wiped out. The few resistant cells, however, quickly repopulate the cancer, causing the treatment to fail.<\/p>\n

\u201cWhether you have resistance prior to the start of treatment was one of the large, outstanding questions associated with this type of treatment,\u201d Bozic said. \u201cOur study offers a quantitative understanding of how resistance evolves, and shows that, because resistance is there at the start, the single-drug therapy won\u2019t work.\u201d<\/p>\n

The answer, Nowak said, is simple: Rather than the one drug used in targeted therapy, treatments must involve at least two drugs.<\/p>\n

Nowak isn\u2019t new to such strategies. In 1995 he participated in a study, also published in Nature, that focused on the rapid evolution of drug resistance in HIV. The result of that study, he said, was the development of the drug \u201ccocktail<\/a>\u201d many HIV-positive patients use to help manage the disease.<\/p>\n

Such a plan, however, isn\u2019t without challenges.<\/p>\n

The treatment must be tailored to the patient, and must be based on the genetic makeup of the patient\u2019s cancer. Perhaps even more importantly, Nowak said, the two drugs used simultaneously must not overlap: If a single mutation allows the cancer to become resistant to both drugs, the treatment will fail just as the single-drug therapy does.<\/p>\n

Nowak estimated that hundreds of drugs might be needed to address all the possible treatment variations. The challenge in the near term, he said, is to develop those drugs.<\/p>\n

\u201cThis will be the main avenue for research into cancer treatment, I think, for the next decade and beyond,\u201d Nowak said. \u201cAs more and more drugs are developed for targeted therapy, I think we will see a revolution in the treatment of cancer.\u201d<\/p>\n\n\n<\/div>\n\n\t\t","protected":false},"excerpt":{"rendered":"

Professor Martin Nowak is one of several co-authors of a paper, published in Nature on June 28,that outlines a new approach to cancer treatment that could make many cancers manageable, if not curable, by overcoming resistance to certain drug treatments. <\/p>\n","protected":false},"author":105622744,"featured_media":113587,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"gz_ga_pageviews":14,"gz_ga_lastupdated":"2018-10-30 21:08","document_color_palette":"crimson","author":"Peter Reuell","affiliation":"Harvard Staff 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Nowak and his team, including Benjamin Allen (right), a postdoctoral fellow in mathematical biology, focused on a multidrug approach to treatment that could make many cancers manageable, if not curable. ","mediaId":113587,"mediaSize":"full","mediaType":"image","mediaUrl":"https:\/\/news.harvard.edu\/gazette\/wp-content\/uploads\/2012\/07\/062512_cancer_cocktail_292_605main.jpg","poster":"","title":"Transforming cancer treatment","subheading":"Multidrug strategy emerges from new research","centeredImage":true,"className":"is-style-full-width-text-below","mediaHeight":403,"mediaWidth":605,"backgroundFixed":false,"backgroundTone":"light","coloredBackground":false,"displayOverlay":true,"fadeInText":false,"isAmbient":false,"mediaLength":"","mediaPosition":"","posterText":"","titleAbove":false,"useUncroppedImage":false,"lock":[],"metadata":[]},"innerBlocks":[],"innerHTML":"<figure class=\"wp-block-image\"><img alt=\"\" height=\"403\" loading=\"eager\" src=\"https:\/\/news.harvard.edu\/gazette\/wp-content\/uploads\/2012\/07\/062512_cancer_cocktail_292_605main.jpg\" width=\"605\"\/><figcaption class=\"wp-element-caption\"><p class=\"wp-element-caption--caption\">\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak (left), director of the Program for Evolutionary Dynamics. Nowak and his team, including Benjamin Allen (right), a postdoctoral fellow in mathematical biology, focused on a multidrug approach to treatment that could make many cancers manageable, if not curable. <\/p><p class=\"wp-element-caption--credit\">Stephanie Mitchell\/Harvard Staff Photographer<\/p><\/figcaption><\/figure>\n","innerContent":["<figure class=\"wp-block-image\"><img alt=\"\" height=\"403\" loading=\"eager\" src=\"https:\/\/news.harvard.edu\/gazette\/wp-content\/uploads\/2012\/07\/062512_cancer_cocktail_292_605main.jpg\" width=\"605\"\/><figcaption class=\"wp-element-caption\"><p class=\"wp-element-caption--caption\">\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak (left), director of the Program for Evolutionary Dynamics. Nowak and his team, including Benjamin Allen (right), a postdoctoral fellow in mathematical biology, focused on a multidrug approach to treatment that could make many cancers manageable, if not curable. <\/p><p class=\"wp-element-caption--credit\">Stephanie Mitchell\/Harvard Staff Photographer<\/p><\/figcaption><\/figure>\n"],"rendered":"<header\n\tclass=\"wp-block-harvard-gazette-article-header alignfull article-header is-style-full-width-text-below centered-image\"\n\tstyle=\" \"\n>\n\t<figure class=\"wp-block-image\"><img alt=\"\" height=\"403\" loading=\"eager\" src=\"https:\/\/news.harvard.edu\/gazette\/wp-content\/uploads\/2012\/07\/062512_cancer_cocktail_292_605main.jpg\" width=\"605\"\/><figcaption class=\"wp-element-caption\"><p class=\"wp-element-caption--caption\">\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak (left), director of the Program for Evolutionary Dynamics. Nowak and his team, including Benjamin Allen (right), a postdoctoral fellow in mathematical biology, focused on a multidrug approach to treatment that could make many cancers manageable, if not curable. <\/p><p class=\"wp-element-caption--credit\">Stephanie Mitchell\/Harvard Staff Photographer<\/p><\/figcaption><\/figure>\n\n\t<div class=\"article-header__content\">\n\t\t\t<a\n\t\t\tclass=\"article-header__category\"\n\t\t\thref=\"https:\/\/news.harvard.edu\/gazette\/section\/health\/\"\n\t\t>\n\t\t\tHealth\t\t<\/a>\n\t\t\n\t\t<h1 class=\"article-header__title wp-block-heading \">\n\t\tTransforming cancer treatment\t<\/h1>\n\n\t\n\t\t\t<\/div>\n\t\t\n\t<div class=\"article-header__meta\">\n\t\t<div class=\"wp-block-post-author\">\n\t\t\t<address class=\"wp-block-post-author__content\">\n\t\t\t\t\t<p class=\"author wp-block-post-author__name\">\n\t\tPeter Reuell\t<\/p>\n\t\t\t<p class=\"wp-block-post-author__byline\">\n\t\t\tHarvard Staff Writer\t\t<\/p>\n\t\t\t\t\t<\/address>\n\t\t<\/div>\n\n\t\t<time class=\"article-header__date\" datetime=\"2012-07-10\">\n\t\t\tJuly 10, 2012\t\t<\/time>\n\n\t\t<span class=\"article-header__reading-time\">\n\t\t\t5 min read\t\t<\/span>\n\t<\/div>\n\n\t\n\t\t\t<h2 class=\"article-header__subheading wp-block-heading\">\n\t\t\tMultidrug strategy emerges from new research\t\t<\/h2>\n\t\t\n<\/header>\n"},"2":{"blockName":"core\/group","attrs":{"templateLock":false,"metadata":{"name":"Article content"},"align":"wide","layout":{"type":"constrained","justifyContent":"center"},"tagName":"div","lock":[],"className":"","style":[],"backgroundColor":"","textColor":"","gradient":"","fontSize":"","fontFamily":"","borderColor":"","ariaLabel":"","anchor":""},"innerBlocks":[{"blockName":"core\/freeform","attrs":{"content":"","lock":[],"metadata":[]},"innerBlocks":[],"innerHTML":"\n\t\t<p>A <a href=\"http:\/\/harvard.edu\">Harvard<\/a> researcher studying the evolution of <a href=\"http:\/\/www.cancerquest.org\/treatment-resistance.html\">drug resistance<\/a> in <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmedhealth\/PMH0002267\/\">cancer<\/a> says that, in a few decades, \u201cmany, many cancers could be manageable.\u201d<\/p>\n<p>\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak, a professor of mathematics and of biology and director of the <a href=\"http:\/\/www.ped.fas.harvard.edu\/\">Program for Evolutionary Dynamics<\/a>. \u201cOne hundred years ago, many people died of bacterial infections. Now, we have treatment for such infections \u2014 those people don\u2019t have to die. I believe we are approaching a similar point with cancer.\u201d<\/p>\n<p>Nowak is one of several co-authors of a paper, published in <a href=\"http:\/\/nature.com\">Nature<\/a> on June 28, that details how resistance to targeted drug therapy emerges in colorectal cancers and describes a multidrug approach to treatment that could make many cancers manageable, if not curable.<\/p>\n<p>The key, Nowak\u2019s research suggests, is to change the way clinicians battle the disease.<\/p>\n<p>Physicians and researchers in recent years have increasingly turned to \u201c<a href=\"http:\/\/www.cancer.gov\/cancertopics\/factsheet\/Therapy\/targeted\">targeted therapies<\/a>\u201d \u2014 drugs that combat cancer by interrupting its ability to grow and spread \u2014 rather than traditional <a href=\"http:\/\/www.mayoclinic.com\/health\/chemotherapy\/MY00536\">chemotherapy<\/a>, but such treatment is far from perfect. Most targeted therapies are effective for only a few months before the cancer evolves resistance to the drugs.<\/p>\n<p>The culprit in the colon cancer treatment examined in the Nature paper is the <a href=\"http:\/\/ghr.nlm.nih.gov\/gene\/KRAS\">KRAS gene<\/a>, which is responsible for producing a protein to regulate cell division. When activated, the gene helps cancer cells develop resistance to targeted-therapy drugs, effectively making the treatment useless.<\/p>\n<p>To better understand what role the KRAS gene plays in drug resistance, a team of researchers led by Bert Vogelstein, the Clayton Professor of Oncology and Pathology at the Johns Hopkins Kimmel Cancer Center, launched a study that began by testing patients to determine if the KRAS gene was activated in their tumors. Patients without an activated KRAS gene underwent a normal round of targeted therapy treatment, and the initial results \u2014 as expected \u2014 were successful. Tests performed after the treatment broke down, however, showed a surprising result: The KRAS gene had been activated.<\/p>\n<p>As part of the research, Vogelstein\u2019s team analyzed a handful of mutations that can lead to the activation of the KRAS gene. To help interpret those results, they turned to Nowak\u2019s team, including mathematicians Benjamin Allen, a postdoctoral fellow in mathematical biology, and <a href=\"http:\/\/www.math.harvard.edu\/%7Eibozic\/\">Ivana Bozic<\/a>, a postdoctoral fellow in mathematics.<\/p>\n<p>Analyzing the clinical results, Allen and Bozic were able to mathematically describe the exponential growth of the cancer and determine whether the mutation that led to drug resistance was pre-existing, or whether it occurred after treatment began. Their model was able to predict, with surprising accuracy, the window of time from when the drug is first administered to when resistance arises and the drug begins to fail.<\/p>\n<p>\u201cBy looking at their results mathematically, we were able to determine conclusively that the resistance was already there, so the therapy was doomed from the start,\u201d Allen said. \u201cThat had been an unresolved question before this study. Clinicians were finding that these kinds of therapies typically don\u2019t work for longer than six months, and our finding provides an explanation for why that failure occurs.\u201d<\/p>\n<p>Put simply, Nowak said, the findings suggest that, of the billions of cancer cells that exist in a patient, only a tiny percentage \u2014 about one in a million \u2014 are resistant to drugs used in targeted therapy. When treatment starts, the nonresistant cells are wiped out. The few resistant cells, however, quickly repopulate the cancer, causing the treatment to fail.<\/p>\n<p>\u201cWhether you have resistance prior to the start of treatment was one of the large, outstanding questions associated with this type of treatment,\u201d Bozic said. \u201cOur study offers a quantitative understanding of how resistance evolves, and shows that, because resistance is there at the start, the single-drug therapy won\u2019t work.\u201d<\/p>\n<p>The answer, Nowak said, is simple: Rather than the one drug used in targeted therapy, treatments must involve at least two drugs.<\/p>\n<p>Nowak isn\u2019t new to such strategies. In 1995 he participated in a study, also published in Nature, that focused on the rapid evolution of drug resistance in HIV. The result of that study, he said, was the development of the drug \u201c<a href=\"http:\/\/www.webmd.com\/hiv-aids\/features\/hiv-aids-treatment\">cocktail<\/a>\u201d many HIV-positive patients use to help manage the disease.<\/p>\n<p>Such a plan, however, isn\u2019t without challenges.<\/p>\n<p>The treatment must be tailored to the patient, and must be based on the genetic makeup of the patient\u2019s cancer. Perhaps even more importantly, Nowak said, the two drugs used simultaneously must not overlap: If a single mutation allows the cancer to become resistant to both drugs, the treatment will fail just as the single-drug therapy does.<\/p>\n<p>Nowak estimated that hundreds of drugs might be needed to address all the possible treatment variations. The challenge in the near term, he said, is to develop those drugs.<\/p>\n<p>\u201cThis will be the main avenue for research into cancer treatment, I think, for the next decade and beyond,\u201d Nowak said. \u201cAs more and more drugs are developed for targeted therapy, I think we will see a revolution in the treatment of cancer.\u201d<\/p>\n","innerContent":["\n\t\t<p>A <a href=\"http:\/\/harvard.edu\">Harvard<\/a> researcher studying the evolution of <a href=\"http:\/\/www.cancerquest.org\/treatment-resistance.html\">drug resistance<\/a> in <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmedhealth\/PMH0002267\/\">cancer<\/a> says that, in a few decades, \u201cmany, many cancers could be manageable.\u201d<\/p>\n<p>\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak, a professor of mathematics and of biology and director of the <a href=\"http:\/\/www.ped.fas.harvard.edu\/\">Program for Evolutionary Dynamics<\/a>. \u201cOne hundred years ago, many people died of bacterial infections. Now, we have treatment for such infections \u2014 those people don\u2019t have to die. I believe we are approaching a similar point with cancer.\u201d<\/p>\n<p>Nowak is one of several co-authors of a paper, published in <a href=\"http:\/\/nature.com\">Nature<\/a> on June 28, that details how resistance to targeted drug therapy emerges in colorectal cancers and describes a multidrug approach to treatment that could make many cancers manageable, if not curable.<\/p>\n<p>The key, Nowak\u2019s research suggests, is to change the way clinicians battle the disease.<\/p>\n<p>Physicians and researchers in recent years have increasingly turned to \u201c<a href=\"http:\/\/www.cancer.gov\/cancertopics\/factsheet\/Therapy\/targeted\">targeted therapies<\/a>\u201d \u2014 drugs that combat cancer by interrupting its ability to grow and spread \u2014 rather than traditional <a href=\"http:\/\/www.mayoclinic.com\/health\/chemotherapy\/MY00536\">chemotherapy<\/a>, but such treatment is far from perfect. Most targeted therapies are effective for only a few months before the cancer evolves resistance to the drugs.<\/p>\n<p>The culprit in the colon cancer treatment examined in the Nature paper is the <a href=\"http:\/\/ghr.nlm.nih.gov\/gene\/KRAS\">KRAS gene<\/a>, which is responsible for producing a protein to regulate cell division. When activated, the gene helps cancer cells develop resistance to targeted-therapy drugs, effectively making the treatment useless.<\/p>\n<p>To better understand what role the KRAS gene plays in drug resistance, a team of researchers led by Bert Vogelstein, the Clayton Professor of Oncology and Pathology at the Johns Hopkins Kimmel Cancer Center, launched a study that began by testing patients to determine if the KRAS gene was activated in their tumors. Patients without an activated KRAS gene underwent a normal round of targeted therapy treatment, and the initial results \u2014 as expected \u2014 were successful. Tests performed after the treatment broke down, however, showed a surprising result: The KRAS gene had been activated.<\/p>\n<p>As part of the research, Vogelstein\u2019s team analyzed a handful of mutations that can lead to the activation of the KRAS gene. To help interpret those results, they turned to Nowak\u2019s team, including mathematicians Benjamin Allen, a postdoctoral fellow in mathematical biology, and <a href=\"http:\/\/www.math.harvard.edu\/%7Eibozic\/\">Ivana Bozic<\/a>, a postdoctoral fellow in mathematics.<\/p>\n<p>Analyzing the clinical results, Allen and Bozic were able to mathematically describe the exponential growth of the cancer and determine whether the mutation that led to drug resistance was pre-existing, or whether it occurred after treatment began. Their model was able to predict, with surprising accuracy, the window of time from when the drug is first administered to when resistance arises and the drug begins to fail.<\/p>\n<p>\u201cBy looking at their results mathematically, we were able to determine conclusively that the resistance was already there, so the therapy was doomed from the start,\u201d Allen said. \u201cThat had been an unresolved question before this study. Clinicians were finding that these kinds of therapies typically don\u2019t work for longer than six months, and our finding provides an explanation for why that failure occurs.\u201d<\/p>\n<p>Put simply, Nowak said, the findings suggest that, of the billions of cancer cells that exist in a patient, only a tiny percentage \u2014 about one in a million \u2014 are resistant to drugs used in targeted therapy. When treatment starts, the nonresistant cells are wiped out. The few resistant cells, however, quickly repopulate the cancer, causing the treatment to fail.<\/p>\n<p>\u201cWhether you have resistance prior to the start of treatment was one of the large, outstanding questions associated with this type of treatment,\u201d Bozic said. \u201cOur study offers a quantitative understanding of how resistance evolves, and shows that, because resistance is there at the start, the single-drug therapy won\u2019t work.\u201d<\/p>\n<p>The answer, Nowak said, is simple: Rather than the one drug used in targeted therapy, treatments must involve at least two drugs.<\/p>\n<p>Nowak isn\u2019t new to such strategies. In 1995 he participated in a study, also published in Nature, that focused on the rapid evolution of drug resistance in HIV. The result of that study, he said, was the development of the drug \u201c<a href=\"http:\/\/www.webmd.com\/hiv-aids\/features\/hiv-aids-treatment\">cocktail<\/a>\u201d many HIV-positive patients use to help manage the disease.<\/p>\n<p>Such a plan, however, isn\u2019t without challenges.<\/p>\n<p>The treatment must be tailored to the patient, and must be based on the genetic makeup of the patient\u2019s cancer. Perhaps even more importantly, Nowak said, the two drugs used simultaneously must not overlap: If a single mutation allows the cancer to become resistant to both drugs, the treatment will fail just as the single-drug therapy does.<\/p>\n<p>Nowak estimated that hundreds of drugs might be needed to address all the possible treatment variations. The challenge in the near term, he said, is to develop those drugs.<\/p>\n<p>\u201cThis will be the main avenue for research into cancer treatment, I think, for the next decade and beyond,\u201d Nowak said. \u201cAs more and more drugs are developed for targeted therapy, I think we will see a revolution in the treatment of cancer.\u201d<\/p>\n"],"rendered":"\n\t\t<p>A <a href=\"http:\/\/harvard.edu\">Harvard<\/a> researcher studying the evolution of <a href=\"http:\/\/www.cancerquest.org\/treatment-resistance.html\">drug resistance<\/a> in <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmedhealth\/PMH0002267\/\">cancer<\/a> says that, in a few decades, \u201cmany, many cancers could be manageable.\u201d<\/p>\n<p>\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak, a professor of mathematics and of biology and director of the <a href=\"http:\/\/www.ped.fas.harvard.edu\/\">Program for Evolutionary Dynamics<\/a>. \u201cOne hundred years ago, many people died of bacterial infections. Now, we have treatment for such infections \u2014 those people don\u2019t have to die. I believe we are approaching a similar point with cancer.\u201d<\/p>\n<p>Nowak is one of several co-authors of a paper, published in <a href=\"http:\/\/nature.com\">Nature<\/a> on June 28, that details how resistance to targeted drug therapy emerges in colorectal cancers and describes a multidrug approach to treatment that could make many cancers manageable, if not curable.<\/p>\n<p>The key, Nowak\u2019s research suggests, is to change the way clinicians battle the disease.<\/p>\n<p>Physicians and researchers in recent years have increasingly turned to \u201c<a href=\"http:\/\/www.cancer.gov\/cancertopics\/factsheet\/Therapy\/targeted\">targeted therapies<\/a>\u201d \u2014 drugs that combat cancer by interrupting its ability to grow and spread \u2014 rather than traditional <a href=\"http:\/\/www.mayoclinic.com\/health\/chemotherapy\/MY00536\">chemotherapy<\/a>, but such treatment is far from perfect. Most targeted therapies are effective for only a few months before the cancer evolves resistance to the drugs.<\/p>\n<p>The culprit in the colon cancer treatment examined in the Nature paper is the <a href=\"http:\/\/ghr.nlm.nih.gov\/gene\/KRAS\">KRAS gene<\/a>, which is responsible for producing a protein to regulate cell division. When activated, the gene helps cancer cells develop resistance to targeted-therapy drugs, effectively making the treatment useless.<\/p>\n<p>To better understand what role the KRAS gene plays in drug resistance, a team of researchers led by Bert Vogelstein, the Clayton Professor of Oncology and Pathology at the Johns Hopkins Kimmel Cancer Center, launched a study that began by testing patients to determine if the KRAS gene was activated in their tumors. Patients without an activated KRAS gene underwent a normal round of targeted therapy treatment, and the initial results \u2014 as expected \u2014 were successful. Tests performed after the treatment broke down, however, showed a surprising result: The KRAS gene had been activated.<\/p>\n<p>As part of the research, Vogelstein\u2019s team analyzed a handful of mutations that can lead to the activation of the KRAS gene. To help interpret those results, they turned to Nowak\u2019s team, including mathematicians Benjamin Allen, a postdoctoral fellow in mathematical biology, and <a href=\"http:\/\/www.math.harvard.edu\/%7Eibozic\/\">Ivana Bozic<\/a>, a postdoctoral fellow in mathematics.<\/p>\n<p>Analyzing the clinical results, Allen and Bozic were able to mathematically describe the exponential growth of the cancer and determine whether the mutation that led to drug resistance was pre-existing, or whether it occurred after treatment began. Their model was able to predict, with surprising accuracy, the window of time from when the drug is first administered to when resistance arises and the drug begins to fail.<\/p>\n<p>\u201cBy looking at their results mathematically, we were able to determine conclusively that the resistance was already there, so the therapy was doomed from the start,\u201d Allen said. \u201cThat had been an unresolved question before this study. Clinicians were finding that these kinds of therapies typically don\u2019t work for longer than six months, and our finding provides an explanation for why that failure occurs.\u201d<\/p>\n<p>Put simply, Nowak said, the findings suggest that, of the billions of cancer cells that exist in a patient, only a tiny percentage \u2014 about one in a million \u2014 are resistant to drugs used in targeted therapy. When treatment starts, the nonresistant cells are wiped out. The few resistant cells, however, quickly repopulate the cancer, causing the treatment to fail.<\/p>\n<p>\u201cWhether you have resistance prior to the start of treatment was one of the large, outstanding questions associated with this type of treatment,\u201d Bozic said. \u201cOur study offers a quantitative understanding of how resistance evolves, and shows that, because resistance is there at the start, the single-drug therapy won\u2019t work.\u201d<\/p>\n<p>The answer, Nowak said, is simple: Rather than the one drug used in targeted therapy, treatments must involve at least two drugs.<\/p>\n<p>Nowak isn\u2019t new to such strategies. In 1995 he participated in a study, also published in Nature, that focused on the rapid evolution of drug resistance in HIV. The result of that study, he said, was the development of the drug \u201c<a href=\"http:\/\/www.webmd.com\/hiv-aids\/features\/hiv-aids-treatment\">cocktail<\/a>\u201d many HIV-positive patients use to help manage the disease.<\/p>\n<p>Such a plan, however, isn\u2019t without challenges.<\/p>\n<p>The treatment must be tailored to the patient, and must be based on the genetic makeup of the patient\u2019s cancer. Perhaps even more importantly, Nowak said, the two drugs used simultaneously must not overlap: If a single mutation allows the cancer to become resistant to both drugs, the treatment will fail just as the single-drug therapy does.<\/p>\n<p>Nowak estimated that hundreds of drugs might be needed to address all the possible treatment variations. The challenge in the near term, he said, is to develop those drugs.<\/p>\n<p>\u201cThis will be the main avenue for research into cancer treatment, I think, for the next decade and beyond,\u201d Nowak said. \u201cAs more and more drugs are developed for targeted therapy, I think we will see a revolution in the treatment of cancer.\u201d<\/p>\n"}],"innerHTML":"\n<div class=\"wp-block-group alignwide\">\n\n\n\n<\/div>\n","innerContent":["\n<div class=\"wp-block-group alignwide\">\n\n","\n\n<\/div>\n"],"rendered":"\n<div class=\"wp-block-group alignwide has-global-padding is-content-justification-center is-layout-constrained wp-block-group-is-layout-constrained\">\n\n\n\t\t<p>A <a href=\"http:\/\/harvard.edu\">Harvard<\/a> researcher studying the evolution of <a href=\"http:\/\/www.cancerquest.org\/treatment-resistance.html\">drug resistance<\/a> in <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmedhealth\/PMH0002267\/\">cancer<\/a> says that, in a few decades, \u201cmany, many cancers could be manageable.\u201d<\/p>\n<p>\u201cMany people are dying needlessly of cancer, and this research may offer a new strategy in that battle,\u201d said Martin Nowak, a professor of mathematics and of biology and director of the <a href=\"http:\/\/www.ped.fas.harvard.edu\/\">Program for Evolutionary Dynamics<\/a>. \u201cOne hundred years ago, many people died of bacterial infections. Now, we have treatment for such infections \u2014 those people don\u2019t have to die. I believe we are approaching a similar point with cancer.\u201d<\/p>\n<p>Nowak is one of several co-authors of a paper, published in <a href=\"http:\/\/nature.com\">Nature<\/a> on June 28, that details how resistance to targeted drug therapy emerges in colorectal cancers and describes a multidrug approach to treatment that could make many cancers manageable, if not curable.<\/p>\n<p>The key, Nowak\u2019s research suggests, is to change the way clinicians battle the disease.<\/p>\n<p>Physicians and researchers in recent years have increasingly turned to \u201c<a href=\"http:\/\/www.cancer.gov\/cancertopics\/factsheet\/Therapy\/targeted\">targeted therapies<\/a>\u201d \u2014 drugs that combat cancer by interrupting its ability to grow and spread \u2014 rather than traditional <a href=\"http:\/\/www.mayoclinic.com\/health\/chemotherapy\/MY00536\">chemotherapy<\/a>, but such treatment is far from perfect. Most targeted therapies are effective for only a few months before the cancer evolves resistance to the drugs.<\/p>\n<p>The culprit in the colon cancer treatment examined in the Nature paper is the <a href=\"http:\/\/ghr.nlm.nih.gov\/gene\/KRAS\">KRAS gene<\/a>, which is responsible for producing a protein to regulate cell division. When activated, the gene helps cancer cells develop resistance to targeted-therapy drugs, effectively making the treatment useless.<\/p>\n<p>To better understand what role the KRAS gene plays in drug resistance, a team of researchers led by Bert Vogelstein, the Clayton Professor of Oncology and Pathology at the Johns Hopkins Kimmel Cancer Center, launched a study that began by testing patients to determine if the KRAS gene was activated in their tumors. Patients without an activated KRAS gene underwent a normal round of targeted therapy treatment, and the initial results \u2014 as expected \u2014 were successful. Tests performed after the treatment broke down, however, showed a surprising result: The KRAS gene had been activated.<\/p>\n<p>As part of the research, Vogelstein\u2019s team analyzed a handful of mutations that can lead to the activation of the KRAS gene. To help interpret those results, they turned to Nowak\u2019s team, including mathematicians Benjamin Allen, a postdoctoral fellow in mathematical biology, and <a href=\"http:\/\/www.math.harvard.edu\/%7Eibozic\/\">Ivana Bozic<\/a>, a postdoctoral fellow in mathematics.<\/p>\n<p>Analyzing the clinical results, Allen and Bozic were able to mathematically describe the exponential growth of the cancer and determine whether the mutation that led to drug resistance was pre-existing, or whether it occurred after treatment began. Their model was able to predict, with surprising accuracy, the window of time from when the drug is first administered to when resistance arises and the drug begins to fail.<\/p>\n<p>\u201cBy looking at their results mathematically, we were able to determine conclusively that the resistance was already there, so the therapy was doomed from the start,\u201d Allen said. \u201cThat had been an unresolved question before this study. Clinicians were finding that these kinds of therapies typically don\u2019t work for longer than six months, and our finding provides an explanation for why that failure occurs.\u201d<\/p>\n<p>Put simply, Nowak said, the findings suggest that, of the billions of cancer cells that exist in a patient, only a tiny percentage \u2014 about one in a million \u2014 are resistant to drugs used in targeted therapy. When treatment starts, the nonresistant cells are wiped out. The few resistant cells, however, quickly repopulate the cancer, causing the treatment to fail.<\/p>\n<p>\u201cWhether you have resistance prior to the start of treatment was one of the large, outstanding questions associated with this type of treatment,\u201d Bozic said. \u201cOur study offers a quantitative understanding of how resistance evolves, and shows that, because resistance is there at the start, the single-drug therapy won\u2019t work.\u201d<\/p>\n<p>The answer, Nowak said, is simple: Rather than the one drug used in targeted therapy, treatments must involve at least two drugs.<\/p>\n<p>Nowak isn\u2019t new to such strategies. In 1995 he participated in a study, also published in Nature, that focused on the rapid evolution of drug resistance in HIV. The result of that study, he said, was the development of the drug \u201c<a href=\"http:\/\/www.webmd.com\/hiv-aids\/features\/hiv-aids-treatment\">cocktail<\/a>\u201d many HIV-positive patients use to help manage the disease.<\/p>\n<p>Such a plan, however, isn\u2019t without challenges.<\/p>\n<p>The treatment must be tailored to the patient, and must be based on the genetic makeup of the patient\u2019s cancer. Perhaps even more importantly, Nowak said, the two drugs used simultaneously must not overlap: If a single mutation allows the cancer to become resistant to both drugs, the treatment will fail just as the single-drug therapy does.<\/p>\n<p>Nowak estimated that hundreds of drugs might be needed to address all the possible treatment variations. The challenge in the near term, he said, is to develop those drugs.<\/p>\n<p>\u201cThis will be the main avenue for research into cancer treatment, I think, for the next decade and beyond,\u201d Nowak said. \u201cAs more and more drugs are developed for targeted therapy, I think we will see a revolution in the treatment of cancer.\u201d<\/p>\n\n\n<\/div>\n"}},"jetpack-related-posts":[{"id":143404,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2013\/07\/new-plan-of-attack-in-cancer-fight\/","url_meta":{"origin":113586,"position":0},"title":"New plan of attack in cancer fight","author":"harvardgazette","date":"July 18, 2013","format":false,"excerpt":"Harvard Professor Martin Nowak and Ivana Bozic, a postdoctoral fellow in mathematics, show that, under certain conditions, using two drugs in a \u201ctargeted therapy\u201d \u2014 a treatment approach designed to interrupt cancer\u2019s ability to grow and spread \u2014 could effectively cure nearly all cancers.","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/07\/071513_cancer_drugs_134_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/07\/071513_cancer_drugs_134_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2013\/07\/071513_cancer_drugs_134_605.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":172889,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2015\/08\/a-fuller-picture-of-cancer\/","url_meta":{"origin":113586,"position":1},"title":"A fuller picture of cancer","author":"harvardgazette","date":"August 28, 2015","format":false,"excerpt":"A research team led by Martin Nowak has developed a model that captures both the shape and speed of tumor growth.","rel":"","context":"In "Science & Tech"","block_context":{"text":"Science & Tech","link":"https:\/\/news.harvard.edu\/gazette\/section\/science-technology\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/08\/n-owak_cancer_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/08\/n-owak_cancer_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2015\/08\/n-owak_cancer_605.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":61740,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2009\/10\/researchers-exploit-genetic-co-dependence-to-kill-treatment-resistant-tumor-cells\/","url_meta":{"origin":113586,"position":2},"title":"Researchers exploit genetic \u2018co-dependence\u2019 to kill treatment-resistant tumor cells","author":"harvardgazette","date":"October 20, 2009","format":false,"excerpt":"Cancer cells fueled by the mutant KRAS oncogene, which makes them notoriously difficult to treat, can be killed by blocking a more vulnerable genetic partner of KRAS, report scientists at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT. The laboratory results, published today online by the\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":116486,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2012\/09\/forward-thinking-on-hiv\/","url_meta":{"origin":113586,"position":3},"title":"Forward thinking on HIV","author":"harvardgazette","date":"September 4, 2012","format":false,"excerpt":"A research team led by Martin Nowak has developed a technique for modeling the effects of various HIV treatments and for predicting whether the treatments will cause the virus to develop resistance.","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2012\/08\/072612_aids__drugs_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2012\/08\/072612_aids__drugs_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2012\/08\/072612_aids__drugs_605.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":113451,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2012\/07\/when-skin-cancer-cells-resist-drug-treatment\/","url_meta":{"origin":113586,"position":4},"title":"When skin cancer cells resist drug treatment","author":"harvardgazette","date":"July 4, 2012","format":false,"excerpt":"Harvard researchers have found that although tailored drugs can eradicate melanoma cells in the lab, they often produce only partial, temporary responses in patients. Researchers have now learned that normal cells that reside within the tumor, part of the tumor microenvironment, may supply factors that help cancer cells grow and\u2026","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2012\/07\/golub_605.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2012\/07\/golub_605.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2012\/07\/golub_605.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":255430,"url":"https:\/\/news.harvard.edu\/gazette\/story\/2018\/10\/harvard-research-targets-cancer-drivers\/","url_meta":{"origin":113586,"position":5},"title":"Study signals a limit to cancer\u2019s complexity","author":"gazettebeckycoleman","date":"October 10, 2018","format":false,"excerpt":"New findings on cancer driver mutations creates hope for targeted therapy. \"It appears there is a limit to cancer\u2019s complexity,\" says one of the study's researchers, Martin Nowak of Harvard University.","rel":"","context":"In "Health"","block_context":{"text":"Health","link":"https:\/\/news.harvard.edu\/gazette\/section\/health\/"},"img":{"alt_text":"Martin Nowak.","src":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2018\/10\/100118_Nowak_OF03.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/news.harvard.edu\/wp-content\/uploads\/2018\/10\/100118_Nowak_OF03.jpg?resize=350%2C200 1x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2018\/10\/100118_Nowak_OF03.jpg?resize=525%2C300 1.5x, https:\/\/news.harvard.edu\/wp-content\/uploads\/2018\/10\/100118_Nowak_OF03.jpg?resize=700%2C400 2x"},"classes":[]}],"jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts\/113586","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/users\/105622744"}],"replies":[{"embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/comments?post=113586"}],"version-history":[{"count":1,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts\/113586\/revisions"}],"predecessor-version":[{"id":267036,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/posts\/113586\/revisions\/267036"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/media\/113587"}],"wp:attachment":[{"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/media?parent=113586"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/categories?post=113586"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/tags?post=113586"},{"taxonomy":"format","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/gazette-formats?post=113586"},{"taxonomy":"series","embeddable":true,"href":"https:\/\/news.harvard.edu\/gazette\/wp-json\/wp\/v2\/series?post=113586"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}