Cancer has a long and challenging history within the human family, with the first instances dating back thousands of years. Although we’ve made progress over the centuries in understanding and treating this disease, it remains a leading cause of death worldwide. Deepening our cancer research is therefore an imperative, especially as our global population continues to grow older. According to the International Agency for Research on Cancer (IARC), an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020.

BGI-Research is committed to improving our understanding of the origins of cancer as well as how best to approach treatment and prevention. As one of the pioneer scientists in cancer research, Dr. Liang WU, Chief Scientist for the Spatio-temporal Pathology Project at BGI-Research, shares her insights on the cause of this disease, why a cure has been elusive, and how Spatio-temporal omics technology can advance our understanding of this critical field of study. 

Dr. Liang WU, Chief Scientist of the Spatio-temporal Pathology at BGI-Research

Q: What causes cancer?

A: In fact, cancer is a generic term for a large group of diseases that can affect any part of the body.

The current cancer classification approach is largely based on the organ where a lesion occurs. The most common types include breast cancer, lung cancer, colorectal cancer, prostate cancer, gastric cancer, and liver cancer. Each cancer type can then be further classified according to the cell type origin and molecular characteristics of the tumor cells. As technologies develop and a more comprehensive understanding of cancer in the medical community becomes available, classification and typing based on molecular characteristics are now widely accepted. The purpose of classification and typing is to select the most appropriate and effective treatment strategies.

One defining feature of cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, which can then invade adjoining parts of the body and spread to other organs - the latter process being known as metastasis. Cancer arises from the transformation of normal cells into tumor cells through a multi-stage process, progressing from a pre-cancerous lesion to a malignant tumor. This transformation also entails a process of accumulating gene mutations, which are the result of genetic factors and external factors. There are three main types of external risk factors: physical, such as ultraviolet rays and ionizing radiation; chemical, including tobacco, alcohol, and aflatoxin, among others; and biological, such as viruses and bacteria infection. For example, more than 99% of cervical cancers are caused by the persistent infection of human papillomavirus (HPV).

Q: Why has it been so complicated for mankind to discover a cure for cancer?

A: People have the impression that cancer treatment is complicated. This view is largely due to many patients being first diagnosed at an advanced stage, resulting in limited treatment options. Most advanced cancers have disseminated and metastasized, making them difficult to eradicate through surgery. Tumor heterogeneity is also an essential factor in drug resistance. The human immune system is an important and powerful defense against cancer, however, after long-term invasion and domestication of the disease, the strength of a patient’s immune system will have been negatively affected to a certain extent. 

Currently, 30%-50% of cancers are preventable by avoiding risk factors and implementing existing evidence-based prevention strategies. In addition, many cancers are more likely to be cured when diagnosed early and treated appropriately. Cancers such as breast, cervical, oral, and colorectal cancers have a high chance of being cured if detected early and treated accordingly. Certain cancers, such as various types of childhood leukemia and lymphoma, have a high cure rate when properly treated, even after the cancer has spread to other parts of the body. 

At present, immunotherapy and its combination therapy have played a positive role in treating various cancers. But which kinds of patients benefit from the therapy? How can we enhance treatment efficiency? And how might we enlarge the beneficiary population? These are big questions that continue to challenge scientists and doctors today.

Q: What's the drawback of current cancer detection?

A: Today, the diagnosis of cancer is a combination of imaging with pathological examination. Early diagnosis and selecting the appropriate cancer treatment will significantly reduce cancer patient mortality rates. In recent years, early cancer detection has been encouraged for cancer prevention, and a series of studies based on circulating tumor DNA, cells, methylation characteristics, and metabolite characteristics have shown the feasibility of this. 

However, bottlenecks still exist. Currently, there is no theoretical basis for predicting the progress of early precancerous lesions. Forming an effective solution post-detection is a major challenge, which also relies on a further understanding of the laws and mechanisms of cancer development.

The occurrence and development of cancer takes place over time. Cancer also involves the uncontrolled and abnormal proliferation, invasion, and migration of tumor cells. The progression of cancer is not only due to cancer cells, but also other critical factors such as the tumor microenvironment, composed of different cell types including fibroblasts and immune cells. The conflict and collaboration of these cell components jointly define the different stages of cancer progression, and treatments are developed for different stages accordingly. Therefore, analyzing this law and its characteristics provides a theoretical basis for understanding cancer prevention and treatment.

Q: In what way will Stereo-seq help overcome the challenges around understanding cancer? 

A: Before the advent of single-cell sequencing technology, we could only test the average expression level of every gene in the cell population, which overlooks the heterogeneity of tumor cells and cannot truly reflect the state of each component in tumor environment. Single-cell technology is a powerful tool for analyzing the heterogeneity of tumor cells and various cell types in a given environment. However, due to the absence of spatial information, interpreting how these cells interact and influence each other remains difficult.

Fortunately, Spatio-temporal Omics technology solved this problem. The advantage of this technology is that it can clearly see the positional relationship and status characteristics between cells. This is very important for understanding the cancer microenvironment, especially regarding the interaction between cells. Combined with the research on different stages of cancer development, Stereo-seq technology can help us better understand how a tumor progresses as well as the local key cell types, characteristics, and factors that are affecting tumor progression. This then provides a reliable theoretical basis and direction for cancer diagnosis, monitoring, and treatment.

Improving patient survival rates as well as their quality of life are two of the most important missions in disease research. Enhancing the sensitivity of early detection of cancer and finding the basis for judging beneficial groups are important methods to improve the survival rate of patients.

The single-cell resolution multi-dimensional quantifiable indicators provided by Stereo-seq make the technology valuable for precise cancer diagnosis and increase our abilities in digital pathology – all of which help in creating effective treatments for patients.