ESMO Press Release: Cancer Outcome Depends on Complex Interactions Between Many Mutations

  • Date: 19 Oct 2017

LUGANO, Switzerland – Cancer outcome depends on complex interactions between many mutations, experts highlighted at the Molecular Analysis for Personalised therapy (MAP) Congress, held 13-14 October in Zurich, Switzerland.

The 2017 meeting focused on two aspects of so-called precision medicine: the complexity of the molecular mechanisms that lead to cancer progression, and the use of technologies to decipher this complexity.

Commenting on the first topic, Prof Fabrice André, co-chair for ESMO of the MAP meeting and Chair of the ESMO Translational Research and Personalised Medicine Working Group, said: “We know now that some cancers need several mutations to grow. Patient outcomes depend on the complex interactions between these mutations.”

During cancer progression, DNA alterations appear randomly in cancer cells. Only the alterations conferring a survival advantage to the cancer cells are 'kept', following the well-known process of natural selection. The survival advantage of a new alteration depends on the alterations already present in the cancer – called ‘evolutionary dependencies’.

A study presented at the MAP Congress aimed to discover these dependencies between alterations and to understand how they affect cancer response to medicines. (1, 2) The researchers looked for patterns in the occurrence of alterations in more than 6,000 patients who had been genetically profiled by The Cancer Genome Atlas (TCGA) consortium. Next, they checked whether the patterns had an impact on how cancer cell lines responded to medicines.

“We found evidence supporting the existence of hundreds of evolutionary dependencies between alterations in cancer,” said lead author Dr Marco Mina, University of Lausanne, Switzerland. “We also found evidence that these evolutionary dependencies affect the response of cancer cell lines to therapy.”

Mina said: “Dependencies between alterations should be considered when deciding on patient therapy as they can have a dramatic impact on response.”

“This study illustrates how the co-occurrence of several mutations can lead to cancer progression,” said André. “Predicting outcome cannot be based on a single mutation. What is important is the overall landscape of mutations.”

Regarding the second topic of technology, André said that scientists know how to sequence DNA; the issues requiring more knowledge are how to transform raw sequencing data into biological information, and how to interpret the clinical meaning of the biological data.

When it comes to transforming raw sequencing data, researchers at the MAP Congress showed how an algorithm they developed, called Excavator2, expands the number of copy number alterations that can be identified by small targeted sequencing panels, and therefore could be targeted for cancer treatment. (3)

Lead author Dr Luca Mazzarella, European Institute of Oncology, Milan, Italy, said: “Our method enhances the identification of alterations, thereby increasing the chances of finding targeted treatments for patients.”

André said: “This study is an example of how we can use bioinformatic tools to fine-tune the analysis of genome sequences.”

“For the third year in a row, the MAP Congress addresses an actual need from the medical and scientific community, who did not benefit, until then, from a place for exchange on personalised medicine,” outlined Prof. Patrice Viens, UNICANER President. “Thanks to a strong partnership between UNICANCER, ESMO and Cancer Research UK (CRUK), this meeting has now become a major event in this domain. We are looking forward to welcoming it again in Paris next year.”

The MAP meeting is a joint initiative of the European Society for Medical Oncology (ESMO), Cancer Research UK and UNICANCER. It gathers medical oncologists, academics, regulators, industry research and development scientists to explore how to make the best use of genome sequencing data to improve personalised treatment of cancer patients.

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Notes to Editors

References

  1. “Interrogating functional dependencies between genomic alterations can facilitate precision medicine approaches in cancer” was presented by Dr Marco Mina, University of Lausanne, Switzerland.
  2. Mina et al. "Conditional selection of genomic alterations dictates cancer evolution and Oncogenic dependencies." Cancer Cell 32.2 (2017): 155-168.
  3. “Genome-wide identification of actionable copy number alterations from targeted sequencing panels with Excavator2” was presented by Dr Luca Mazzarella, European Institute of Oncology, Milan, Italy.

About the European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With 17,000 members representing oncology professionals from 150 countries worldwide, ESMO is the society of reference for oncology education and information, committed to supporting our members to develop and advance in a fast-evolving professional environment.

About Cancer Research UK

Cancer Research UK (CRUK) is the largest independent funder of cancer research in the world. Every year CRUK invest around £350 million in world-leading research and innovative ideas that they believe will have the greatest impact for the public and cancer patients. CRUK’s vision is to bring forward the day when all cancers are cured by supporting excellent research as well as influencing policy, providing information and empowering the public to ensure that the outputs of research are adopted. This work is almost entirely funded through the generosity of the public. CRUK partner with a range of organisations, ensuring that cancer is tackled on a global stage.

www.cancerresearchuk.org

About Unicancer

UNICANCER, a major player in oncology, groups together the 20 French Comprehensive Cancer Centers (FCCC). They are private, non-profit health establishments exclusively dedicated to care, research and education in cancer (+ 135,000 patients hospitalized every year, + 500 ongoing clinical trials promoted by one or several FCCC)

Our research priorities:

  1. develop innovative research into targeted therapies and immunotherapy programs
  2. promote clinical research in areas neglected by the pharmaceutical industry (e. g. rare cancers, pediatric & elderly populations, surgery, radiotherapy, supportive care)
  3. encourage translational research (systematic biobanking with open access for research)
  4. optimize therapeutic sequences according to prognostic criteria
  5. investigate treatment response, toxicities and resistance through large cohort studies

www.unicancer.fr

This press release contains information provided by the authors of the highlighted abstracts. It does not necessarily reflect the views or opinions of ESMO, UNICANCER or CRUK who cannot be held responsible for the accuracy of the data.