Tag: cancer research

Non-genetic Theories of Cancer Address Inconsistencies in Current Paradigm

A recent essay argues for re-considering cancer as a genetic disease

3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: Sriram Subramaniam/ National Cancer Institute

It’s time for researchers to reconsider the current paradigm of cancer as a genetic disease, argued Sui Huang from the Institute for Systems Biology, USA, and colleagues in a new essay published March 18th in the open-access journal PLOS Biology.

The prevailing theory on the origin of cancer is that an otherwise normal cell accumulates genetic mutations that allow it to grow and reproduce unchecked. This paradigm has driven large-scale cancer genome sequencing projects, such as The Cancer Genome Atlas, to identify cancer-driving mutations and develop drugs designed to target aberrant proteins and pathways.

In their new essay, Huang and colleagues argue that this somatic mutation theory of cancer is unproductive. They point to inconsistencies in the sequencing data that contradict the current theory, including the fact that many cancers have no known driver mutations while some normal tissues can harbour cancer-causing mutations.

They propose a broader, more “holistic” view that embraces organismal biology and theory. Specifically, they encourage considering alternative paradigms that encompass non-genetic processes involved in tumorigenesis. For example, they explain the concepts of cancer as a result of disruptions in gene regulatory networks (Huang) — or of tissue organisation, a theory that considers the disturbance of the field generated by neighbouring cells and surrounding tissue (Soto-Sonnenschein). The authors argue that these alternative explanations will guide experiments to advance our understanding of the origins of cancer.

The authors add: “A full embrace of the idea that the origin of cancer lies beyond the realm of genetic mutations will open new vistas on cancer treatment and prevention.  Accepting that not all carcinogens are mutagens will strengthen public health policies aimed to prevent exposure to environmental non-mutagenic factors that may promote cancer, such as food additives and plastics and many other toxicants that alter tissue homeostasis.”

Provided by PLOS

How Cancer Reprograms Immune Cells to Join the Enemy

Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

Cancer has been described as “a wound that does not heal,” implying that the immune system is unable to wipe out invading tumour cells. A new discovery reported in PNAS confirms that a key molecule can reprogram immune cells into turncoats that promote cancer growth.

Studying the behaviour of these “pro-tumour” immune cells is important because they could be targets for therapies that block their harmful activity, said Minsoo Kim, PhD, corresponding author of the study and a research leader at the Wilmot Cancer Institute.

Kim led a team of scientists investigating the dynamic interactions that occur between cells in the tumor environment, and the underlying factors that cause the harmful transformation of immune cells from good to bad.

They found that PAF (platelet-activating factor) is the key molecule that controls the destiny of the immune cells. PAF not only recruits cancer-promoting cells, but it also suppresses the immune system’s ability to fight back. In addition, they found that multiple cancers rely on the same PAF signals.

“This is what could be most significant,” said Kim. “Because if we find a treatment that could interfere with PAF, it could potentially apply to many types of cancer.”

Much of the team’s work focused on pancreatic cancer cells. It is one of the most deadly cancers, with a five-year survival rate of about 12%, and is notoriously hard to treat because pancreatic tumours are surrounded by a toxic stew of proteins and other tissues that protect the cancer from the immune system’s natural role to attack invaders. They also studied breast, ovarian, colorectal, and lung cancer cells, using advanced 3D imaging technology to watch the behaviour of immune cells as they swarmed to the cancerous region.

Source: University of Rochester Medical Center