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Cracking the cancer code: a personalised genomic approach
Cancer and Society
Documentaries Cracking the cancer code: a personalised genomic approach
www.thelancet.com/oncology Vol 18 June 2017
expression of a growth factor in her cancer cells that could be blocked with a drug commonly used for diabetes. Scrivens has become a poster child for the programme, but, as Dr Stephen Chia, a medical oncologist at the BC Cancer Agency, is at pains to stress, “POG does not provide miracles, it offers insights into what might be driving or not,” helping to indicate a path for possible treatment. Fewer than 5% of participants turn out to be ‘super responders’, and while only less than 40% experience improved outcomes, some relapse, others do not respond to treatment, and about 25% do not have any remedial approach indicated by their genomic analysis. In an unobtrusive ‘observational’ style, we are privy to the intimate medical lives of several participants at various stages of the POG programme, illustrating this diversity of outcomes, but also the day-to-day disruption, anxiety, and drama of experiencing cancer diagnosis and treatment. Trish Keating, initially classed as a ‘super responder’ when her cancer disappeared after a course of blood pressure medication, is found to be relapsing, and a second POG analysis reveals the cancer developed resistance to the drug. When we return to her story, we learn that she has responded positively to an increase in dose. When Jen Strack, diagnosed with stage 4 lung cancer, enrols in the POG trial, her analysis shows an unusual genetic fusion that produces very high levels of a protein driving her cancer, and while a drug exists to target the protein, until Strack’s case, no patient had yet been found to test its activity. The treatment programme, at least for some time, sends her cancer into remission, and, as the first genefusion case of its kind, it represents a breakthrough in oncogenomics. All of these new insights about cancer drivers feed into a POG database
of information on genetic behaviour in cancer. While resource-hungry genomic analysis is unlikely to become standard procedure for individual patients with cancer, the cost has fallen majorly in the past 5 years, from CAN$250 000 to around CAN$20 000. Programme co-leader Dr Marco Marra predicts a future where with “100 000 fully characterised genomes, complete with outcome information…[you could] have a resource that might revolutionise how we develop drugs.” 5 years and 750 enrolments into the programme, Laskin does not expect POG to provide a cure for cancer, but she does hope for a future where cancer has become “a chronic disease with tolerable treatments”. Measured against this goal, POG has been successful in buying some participants time with the help of manageable drugs. But beyond this, a genomic approach could represent an important step in a major shift from the traditional classification of cancer towards a highly individualised understanding of the disease under the banner of personalised medicine. In presenting an accessible, detailed, and balanced look at the work of the POG team, The Nature of Things is doing valuable public engagement work at the cutting edge of cancer research.
Cracking Cancer Directed by Judith Pyke 2017, 45 min For more on the POG trial see http://www.bcgsc.ca/project/ pog
Catherine Lucas
Dreamfilm
In a February, 2017, episode of Canada’s flagship science series The Nature of Things, presenter David Suzuki outlines “a revolutionary new approach to cracking cancer”—one that puts genomic analysis at the heart of diagnosis and treatment. In Cracking Cancer, viewers witness the inner workings of a medical trial at the BC Cancer Agency in Vancouver (BC, Canada), and follow the intimate stories of participants as they test out a new personalised approach that promises to change not only the way we treat, but also the way we think, about cancer. Cancer is categorised according to where it occurs in the body. Project co-founder Dr Janessa Laskin is working on an approach that will cut across existing divisions and re-organise cancer into “hundreds, maybe thousands of diseases,” thus presenting a new set of remedial possibilities. This is achieved with the help of a new diagnostic system called Personalised OncoGenomics (POG). Using immense computer power, each participant’s genome is mapped twice, once using their normal cells, and again with biopsied cancer cells. These DNA and RNA sequences are then compared to reveal the precise breakages and mutations driving the cancer. Interdisciplinary teams of geneticists, scientists, and doctors from across the spectrum of cancer specialties examine and discuss the genomic abnormalities found. For each participant, this culminates in a search for drugs that might block the cancer drivers so that a long-term programme of treatment can be prescribed. The documentary begins with the story of ‘super responder’ Zuri Scrivens, the 10th patient to participate in the POG trial, after her breast cancer spread to her liver and lymph nodes. Scrivens made a full recovery when POG revealed very high
Zuri Scrivens and Dr Janessa Laskin
717
Documentaries Cracking the cancer code: a personalised genomic approach
www.thelancet.com/oncology Vol 18 June 2017
expression of a growth factor in her cancer cells that could be blocked with a drug commonly used for diabetes. Scrivens has become a poster child for the programme, but, as Dr Stephen Chia, a medical oncologist at the BC Cancer Agency, is at pains to stress, “POG does not provide miracles, it offers insights into what might be driving or not,” helping to indicate a path for possible treatment. Fewer than 5% of participants turn out to be ‘super responders’, and while only less than 40% experience improved outcomes, some relapse, others do not respond to treatment, and about 25% do not have any remedial approach indicated by their genomic analysis. In an unobtrusive ‘observational’ style, we are privy to the intimate medical lives of several participants at various stages of the POG programme, illustrating this diversity of outcomes, but also the day-to-day disruption, anxiety, and drama of experiencing cancer diagnosis and treatment. Trish Keating, initially classed as a ‘super responder’ when her cancer disappeared after a course of blood pressure medication, is found to be relapsing, and a second POG analysis reveals the cancer developed resistance to the drug. When we return to her story, we learn that she has responded positively to an increase in dose. When Jen Strack, diagnosed with stage 4 lung cancer, enrols in the POG trial, her analysis shows an unusual genetic fusion that produces very high levels of a protein driving her cancer, and while a drug exists to target the protein, until Strack’s case, no patient had yet been found to test its activity. The treatment programme, at least for some time, sends her cancer into remission, and, as the first genefusion case of its kind, it represents a breakthrough in oncogenomics. All of these new insights about cancer drivers feed into a POG database
of information on genetic behaviour in cancer. While resource-hungry genomic analysis is unlikely to become standard procedure for individual patients with cancer, the cost has fallen majorly in the past 5 years, from CAN$250 000 to around CAN$20 000. Programme co-leader Dr Marco Marra predicts a future where with “100 000 fully characterised genomes, complete with outcome information…[you could] have a resource that might revolutionise how we develop drugs.” 5 years and 750 enrolments into the programme, Laskin does not expect POG to provide a cure for cancer, but she does hope for a future where cancer has become “a chronic disease with tolerable treatments”. Measured against this goal, POG has been successful in buying some participants time with the help of manageable drugs. But beyond this, a genomic approach could represent an important step in a major shift from the traditional classification of cancer towards a highly individualised understanding of the disease under the banner of personalised medicine. In presenting an accessible, detailed, and balanced look at the work of the POG team, The Nature of Things is doing valuable public engagement work at the cutting edge of cancer research.
Cracking Cancer Directed by Judith Pyke 2017, 45 min For more on the POG trial see http://www.bcgsc.ca/project/ pog
Catherine Lucas
Dreamfilm
In a February, 2017, episode of Canada’s flagship science series The Nature of Things, presenter David Suzuki outlines “a revolutionary new approach to cracking cancer”—one that puts genomic analysis at the heart of diagnosis and treatment. In Cracking Cancer, viewers witness the inner workings of a medical trial at the BC Cancer Agency in Vancouver (BC, Canada), and follow the intimate stories of participants as they test out a new personalised approach that promises to change not only the way we treat, but also the way we think, about cancer. Cancer is categorised according to where it occurs in the body. Project co-founder Dr Janessa Laskin is working on an approach that will cut across existing divisions and re-organise cancer into “hundreds, maybe thousands of diseases,” thus presenting a new set of remedial possibilities. This is achieved with the help of a new diagnostic system called Personalised OncoGenomics (POG). Using immense computer power, each participant’s genome is mapped twice, once using their normal cells, and again with biopsied cancer cells. These DNA and RNA sequences are then compared to reveal the precise breakages and mutations driving the cancer. Interdisciplinary teams of geneticists, scientists, and doctors from across the spectrum of cancer specialties examine and discuss the genomic abnormalities found. For each participant, this culminates in a search for drugs that might block the cancer drivers so that a long-term programme of treatment can be prescribed. The documentary begins with the story of ‘super responder’ Zuri Scrivens, the 10th patient to participate in the POG trial, after her breast cancer spread to her liver and lymph nodes. Scrivens made a full recovery when POG revealed very high
Zuri Scrivens and Dr Janessa Laskin
717