From genomic medicine, a revolution rolls towards cancer care | Explained


A microscopic image of breast cancer cells obtained at the U.S. National Cancer Institute in September 8, 2021. Cancer is a disease of the genome, and certain inherited variants of genes form the basis of hereditary cancers like breast cancer.
| Photo Credit: NCI/Unsplash

Cancer has emerged as a major public health concern worldwide with about 20 million new patients being added every year. The World Health Organisation has estimated the cancer burden will increase by almost 60% over the next decade, potentially rendering it the second major cause of death. India alone adds approximately 1.4 million new cancer cases every year, with almost 1 in 1,000 Indians being diagnosed annually, per the National Cancer Registry.

Cancer is a disease of the genome. It is caused by changes in genes that cause some cells to divide in an uncontrolled way. These changes can be inherited or acquired. Inherited genetic variants form the basis of many hereditary cancers, including breast and ovarian cancer. Advancements in genomic technologies in the last couple decades, including global initiatives like the Cancer Genome Atlas, have provided a shot in the arm to understand the molecular underpinnings of cancer, which in turn have yielded a new generation of therapies that target molecular defects.

Precision oncology

Such therapies are called precision oncology therapies. Their eligibility in a given setting is determined by molecular tests. Of the 200-odd therapies the U.S. Food and Drug Administration has approved, almost a third have a DNA-based test as biomarker. And while scientists are discovering new biomarkers for cancers, the focus of late has been shifting to understand how genomic tests could become the mainstay of cancer treatment in clinical settings.

As part of the U.K.’s ongoing ‘100,000 Genome Program’, a study of over 13,800 cancer patients, published last week, suggested cancer genomics could indeed transform cancer care. The programme reportedly demonstrated that genome sequencing integrated with routine clinical data could render cancer treatments more customisable. The implications of this study extend far beyond the boundaries of current practice of medicine, and mark a leap forward in the era of precision oncology.

At the heart of this transformation lies whole-genome sequencing (WGS), a tool that can sequence a person’s DNA in its entirety – i.e. all 3.2 billion nucleotides – in a single comprehensive test. The sequencing and in-depth analysis don’t treat the genome (derived from the blood) in isolation; instead, they happen together with the sequence of the genome obtained from cancerous tissue or a tumour.

Insights into cancer

In the U.K.-wide study, researchers obtained, sequenced, and analysed the genomes of people with different types of cancers; the genomes came from blood and tumour tissues. Their analysis revealed details that the researchers have said can be applied in clinical settings to guide treatment strategies for cancer patients.

Notably, according to the study, a higher fraction of individuals diagnosed with brain tumours as well as those dealing with bowel or lung cancers had distinct DNA changes that could become new targets for therapy. The study also provided novel insights that could reshape even our understanding of challenging conditions like ovarian cancers and sarcomas.

For example, approximately 10% of sarcomas (rare cancers of the bone and soft tissue) exhibited genetic changes that could impact treatment decisions. The researchers also identified a corresponding proportion of ovarian cancers as being potentially inherited.

Consequences of genomic medicine

The impetus behind this study aligns with the vision of England’s public health system. The National Health Service (NHS) in particular has been keen on understanding how genomic medicine can be harnessed to enhance cancer care. The study also signifies the realisation of the promise of precision medicine, envisioned almost a decade ago with the launch of the population-scale ‘100,000 Genomes Project’, in which patients were recruited as part of a larger genomics initiative whose focus was as much cancer as rare genetic diseases.

The lessons learned from this large study are already finding real-world application in some parts of the U.K. Hospital trusts in East Midlands are incorporating insights from preemptive genome-sequencing and referring individuals with certain genetic mutations to clinical trials for certain therapies or steering clear of treatments or modifying the dosages of therapies that might potentially result in adverse side-effects. This underscores the immediate impact of groundbreaking genomics research: on implementing patient care in clinical settings.

But amid the optimism surrounding this breakthrough study, many researchers have also advised caution and urged a more nuanced perspective on the consequences of genomic medicine. One crucial consideration is the use of information gleaned from whole-genome sequencing in practice – especially in a scenario where, say, a particularly harmful genetic change has been identified in an individual but for which there are no treatments available.

Shifts in clinical testing

Fortunately, advances in precision oncology therapies are rapidly closing this gap. Research is moving towards a more comprehensive understanding of tumours, one that integrates genomics, along with studies on proteins and metabolites in the body – also known as ‘multi-omics’. At the same time, it is gaining wider application in identifying newer molecular subtypes of cancer with implications for cancer progression and treatment. However, integrating these new insights into clinical care will require a paradigm shift in clinical testing as it exists.

In sum, while the new study is a milestone in genomics and genomic medicine, we can see why it will also spark a broader conversation on the nuances of integrating genomics and genomics-guided treatments into the standard protocols of cancer care. As lessons from genomics research into oncology continue to unfold, it opens up new horizons, opportunities and – unmistakably – challenges. Research from such studies will lay the foundation for a future where genomics insights and evidence can seamlessly inform clinical decision-making on the population-scale.

The authors are senior consultants at Vishwanath Cancer Care Foundation and adjunct professors at the Indian Institute of Technology, Kanpur. All opinions expressed here are personal.

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