Taming the Complexity of Cancer

For every White person of European descent with natural killer T-cell lymphoma (NKTCL), up to five Asians will be diagnosed with the same disease.

Though aggressive, NKTCL is typically a rare type of cancer, so its unusually high rates in Asian populations have baffled scientists and doctors for years. The persistent underrepresentation of Asians in large-scale genetic studies left this puzzle unsolved—that is until 2020, when researchers from various countries in Asia conducted the largest genetic study on NKTCL to date, enrolling more than 20,000 participants, all of East Asian ethnicity.

Because of these efforts, NKTCL has become part of a small but growing list of cancers that had genetic characteristics unique to Asian populations. In the same year, at least two other studies published similar findings: one revealed that lung adenocarcinomas mutated much slower in Asians, while another discovered gene mutations that made Asian alcohol drinkers more susceptible to gastric cancer.

Cancer has always been understood as a complicated disease. But as these studies have shown, the more we learn about it, the depth of its complexity also becomes more apparent. Soon, a blanket approach to diagnosing and treating malignancies won’t cut it. To keep up with cancer, the medical community will need more sophisticated, precise tools.

In this feature, we look at precision oncology as an emerging strategy that promises more accurate diagnoses and effective treatment—paving the way for a new paradigm in cancer care.

Cracking the Cancer Conundrum

By using molecular profiling techniques to characterise tumours and to optimise treatment, precision oncology is medicine’s answer to cancer’s complexity. Though its exact definition has evolved through the years, precision oncology strategies have always acknowledged the central role of genetics in the development, progression and management of malignancies.

In fact, genetic analysis is a cornerstone of precision oncology. In some cancers, the presence or absence of a particular genetic mutation could indicate its aggressiveness, with many doctors already taking this information into consideration when delivering diagnoses. However, the true promise of precision oncology lies in its potential to completely overhaul cancer treatment.

Currently, malignancies are treated with a ‘one-size-fits-all’ approach. Chemotherapy, radiotherapy and surgery are the three main pillars of cancer treatment and are applied regardless of disease stage or type. While there is some flexibility, such as foregoing surgery in frail patients or adjusting drug choice based on allergies, the overall regimen remains rigid.

The result? Inefficient cancer care. Patients and doctors often have to suffer through a painful trial-and-error phase before they settle on the most effective treatment regimen, all while racking up healthcare costs and side effects.

In contrast, precision oncology uses state-the-art technologies to ensure efficiency. With the help of advanced gene sequencing techniques and powerful analytics software, doctors can look for genes, proteins and other similar markers that could reveal key weaknesses and susceptibilities of the tumour.

This information, in turn, can help them prescribe drugs with a high likelihood of success. In cases where there are simply no known effective treatments, doctors can also use biomarker data to enrol their patients into the most appropriate clinical trial.

Moreover, precision oncology also accounts for the patient’s specific genetic and molecular profile, allowing doctors to choose medicines that are unlikely to have heavy side-effects.

In sum, precision oncology harnesses deep molecular data and combines it with patient information—from their lifestyles and ethnicities to their medical histories and environmental exposures—to arrive at the optimal treatment plan.

The Future is Now

While precision oncology is touted as the future of cancer medicine, many cancers are already benefitting from a precision approach.

Perhaps the most prominent example is non-small cell lung cancer (NSCLC). Traditionally, this malignancy had few treatment options, with most patients relying on highly toxic platinum-based chemotherapy. But today, precision oncology dominates clinical decision-making for NSCLC, heavily influencing treatment choices for up to half of patients and resulting in better outcomes.

Some of the more extensively-studied forms of cancer, like breast cancer and gastric cancer, have also benefitted from a precision oncology approach by using markers that have already been identified and validated.

But precision oncology is still very young. Though the list is growing, there is still only a small number of cancers that benefit from a precision approach, with drugs that can target these malignancies. In non-White ethnic groups, basic mutation data can be sparse, making even precision diagnosis difficult. These gaps will need to be thoroughly addressed before precision oncology can truly and completely be integrated into clinical practice.

Thankfully, the field is exciting and rapidly evolving. Researchers are continuously discovering new genetic alterations and biomarkers that could act as therapeutic targets and developing new technologies to smoothen the process for patients. As we become equipped with better data and more advanced techniques, cancer treatment can someday become less daunting—with the help of precision oncology.

References:

1. Lin, G.W., Xu, C., Chen, K., Huang, H.Q., Chen, J., et al. Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study in multiple populations. The Lancet Oncology 21, 306-316 (2020)

2. Brown, N.A., Aisner, D.L., Oxnard, G.R. Precision Medicine in Non–Small Cell Lung Cancer: Current Standards in Pathology and Biomarker Interpretation. American Society of Clinical Oncology Educational Book 38, 708-715 (2018)

3. Schwartzberg, L., Kim, E.S., Liu, D., Schrag, D., Precision Oncology: Who, How, What, When, and When Not? American Society of Clinical Oncology Educational Book 37, 160-169 (2018)

4. Bassig, B. A., Au, W.Y., Mang, O., Ngan, R., Morton, L.M., et al. Subtype-specific incidence rates of lymphoid malignancies in Hong Kong compared to the United States, 2001–2010. Cancer Epidemiology 42, 15-23 (2016)