The use of genomics is changing how the medical sector diagnoses and manages cancer with tissue pathologists lying at the forefront of this evolution, a new review by Australian scientists has found.

The review1, published in the journal Pathology in October, scoured through around 130 papers to work out precisely how cancer genomics — the study of how DNA and gene expression differs between cancerous and normal cells — had changed over time and how the role of the humble tissue pathologist had evolved along with these trends.

Lead author and anatomical pathologist Dr Sowmya Sharma of the Faculty of Medicine at University of Queensland uncovered how genomic advances have helped pathologists move from assisting on the sidelines to taking up a more central role when it comes to treating and managing cancer.

Tissue pathology is rapidly adapting to incorporate genomic changes detected in cancer into its routine reporting. Indeed tissue pathologists will participate in multidisciplinary tumour boards to deliver specific pathological insights to result in patient-specific treatments, follow-up and disease prevention. The role of the tissue pathologist will then shift from a current, mainly supportive role to a truly clinical realm,” she told Lab Down Under.

These changes are possible because the cost of genomics has been exponentially decreasing and has come a long way since the Human Genome Project took 13 years to complete, costing US$13 billion. These days, commercial whole genome sequencing costs just over US$1,000 and has an average turnaround time of around seven days.

“Molecular pathology will become the tool to specifically determine the individual cancer pathophysiology, hence delivering personalised medicine to patients with cancer. Once incorporated as an integral part of screening, diagnosis and follow-up of human cancer in the near future, democratisation of availability and accessibility of personalised medicine and personalised pathology to the entire population would be possible,” Dr Sharma wrote in the paper.

Building a foundational review

As an anatomical pathologist with more than 10 years of experience in the field, Dr Sharma has built a fascination with genomics in cancer over her career, and has used that interest to pursue a PhD on the subject at the University of Queensland.

The review is the first step to a wider PhD which will explore methods of targeting lung and oesophageal cancers through methods such as fine needle aspiration cytology, machine learning algorithms and circulating tumour DNA.

A fundamental understanding of the evolution of cancer genomics was essential to design my PhD projects. Additionally, there are sections within the review article (e.g. sections on lung and oesophageal cancers, on immunotherapy and on novel cancer follow-up approaches) that raise important research questions, which are connected to the answers revealed through the above projects,” she said.

To compile the review, Dr Sharma used the library resources at UQ to examine current trends, recent advances and future predictions for tissue pathologists as well as finding papers which justified her PhD.

Moving towards personalised medicine

The review focused on what is called ‘precision’ diagnostics: a precise, targeted form of patient treatment that is a more modern approach than the traditional, general care given to cancer patients in the past.

The usual trend in oncology is that symptoms lead to investigations (pathology) followed by treatment. This is a rather generalised approach to healthcare in a given population,” Dr Sharma said.

At the turn of the millennium, the human genetic code was deciphered and led to exploration of personalised healthcare for individuals. This personalisation depends upon identifying, through pathological investigations, key genomic targets that are amenable to specific treatments; now termed precision pathology or personalised pathology.

According to the paper, precision medicine could potentially deliver successful tumour remission and better quality of life for patients. As well as identifying the tumour and any “actionable variants” in the cancer genome, it can help clinicians and tissue pathologists customise treatment and monitoring to specific patients.

“This manner of investigation, although partially tissue-agnostic, is transforming long-term treatment and management of most well-known cancers, especially the poorly differentiated/undifferentiated diagnoses that portend a gloomy future for their patients,” Dr Sharma wrote in the paper.

“Whilst a ‘one patient – one treatment’ paradigm may never become economically viable, a greater emphasis on further typing and subtyping of tumours is becoming popular, limiting adverse effects from non-specific treatment options that particular patients would be non-responsive to, and suggesting specific treatments that may be more effective.”

‘Cancer will be curable one day

Almost 50 per cent of the cost of healthcare generally stems from terminal illnesses such as cancer. Dr Sharma told Lab Down Under that equipping tissue pathologists with better tools for precision medicine to treat cancer via approaches such as molecular diagnosis to identify unknown cancers, assess cancer stage to predict prognosis and survival, and subtype tumours for personalised therapeutics could help reduce the mortality rate of cancer.

Despite scientific advancements in oncology, the proportion of cancers that can be cured remains tiny. With precision pathology and precision oncology, cancer will be curable one day,” she said.

Then, cancer will be reduced to a waxing-waning illness that can be treated/controlled like diabetes and hypertension, at home with cost-effective, patient specific drugs with minimal adverse effects. We can then assume that medicine has indeed been personalised.

This transition for tissue pathologists was slow but decisive, Dr Sharma said, predicting that there would be much more integration of the pathology role in the future.

“Whilst traditional anatomical pathology will continue to play a significant role in tissue diagnosis of cancer, especially the surgically curable tumours (colorectal cancers, melanocytic and non-melanocytic skin cancers, etc), a transformative shift is impending and inevitable in the diagnosis, treatment, follow-up and management of advanced, recurrent and metastatic lesions, in primary cancers of solid organs that pose significant risk from surgical manipulation, and in cancer prevention,” she wrote.

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1 Sharma S, George P, Waddell N. Precision diagnostics: Integration of tissue pathology and genomics in cancer. Pathology, 2021 Oct 8, S0031-3025(21)00471-2.

Featured image: Microscope Research Lab Scientific. Picture by MaxPixel. Used under the Creative Commons CC0 Public Domain licence.

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