Gamechanging breast cancer discovery reverts cancer cells into normal cells

[July 5, 2023: Staff Writer, The Brighter Side of News]

Breast cancer has always been a complex disease, defined by the relentless proliferation of cells, their adaptability to various environmental changes, and an insidious capability to resist conventional treatment strategies.

Cancer cells' modus operandi is quite similar to that of stem cells or those in an early maturation phase, with an uncanny knack for survival and propagation. With this perplexing characteristic, a team of researchers at the University of Basel and the University Hospital Basel in Switzerland have embarked on an intriguing journey of discovery: turning these cancer cells into a more benign version of themselves through a process known as differentiation.

Differentiation, a therapeutic strategy, involves artificially maturing cancer cells to take on a form similar to that of normal cells. Despite its successful application in blood-borne cancers, differentiation therapy has not been thoroughly explored for solid tumors.

But a recent publication in the journal Oncogene has breathed new life into the potential of this approach for treating particularly aggressive types of carcinoma such as triple-negative breast cancer. "We show here that we can convert breast cancer cells to less harmful cells that stop growing," revealed Professor Mohamed Bentires-Alj, a group leader at the Department of Biomedicine, and the head of this ground-breaking research project.

Related Stories:

The potent capabilities of the hormone estrogen were instrumental in this study. The hormone, renowned for its wide array of biological effects, operates by binding to the estrogen receptor within the cells. Interestingly, in normal breast cells, estrogen receptor expression indicates maturity and specialization, essentially halting the cell's ability to proliferate.

However, this mechanism takes a nefarious turn in certain breast cancers, where cells expressing the estrogen receptor proliferate substantially. These cases, known as estrogen receptor-positive breast cancers, constitute approximately 75% of all breast cancer diagnoses. The cancer's susceptibility to estrogen and its receptor allows for the application of anti-estrogenic therapies, which have proven to be remarkably successful in treatment.

In stark contrast, the triple-negative subtype, a particularly aggressive form of the disease, is impervious to both estrogens and anti-estrogens. Predominantly affecting pre-menopausal women, this subtype poses a daunting challenge for oncologists due to the scarcity of effective treatment options.

Inspired by the possibility of manipulating cellular mechanisms, Dr. Milica Vulin, the study’s lead author, shared, "Our initial idea was to induce estrogen receptor expression in order to convert triple-negative breast cancer into estrogen-receptor positive breast cancer because of more effective treatment options available for this subtype."

To accomplish this audacious feat, the team, in collaboration with global healthcare company Novartis, embarked on a rigorous screening process of over 9500 compounds to identify potential candidates capable of triggering estrogen receptor expression. The compounds yielding the most promising results were inhibitors of polo-like kinase 1 (PLK1), an essential cell cycle protein.

The inhibition of PLK1 not only increased estrogen receptor expression but also led to a surprising revelation. The once lethal triple-negative breast cancer cells were not just transformed into a more manageable cancer subtype but were effectively converted into cells reminiscent of normal cells.

Such a monumental discovery underscores the potential for a paradigm shift in the approach to cancer treatment. Bentires-Alj pointed out, "Understanding the cellular and molecular mechanisms that define cancer and how these mechanisms differ from normal cells is crucial for developing new innovative therapies."

The findings of this study open up exciting prospects for treating triple-negative breast cancer. "The compounds used in this study are already in clinical trials to treat other cancer types, including blood-borne, lung, and pancreatic cancer," the researcher added, emphasizing the feasibility of testing these compounds in breast cancer treatment.

Immunotherapies, heralded as the dawn of a new era in cancer treatment, operate on the principle that "normal-like" cells can be eliminated by the immune system, while "cancerous" cells manage to dodge the immune cell onslaught. The question, therefore, arises: could differentiation therapy be successfully combined with immunotherapies?

As Bentires-Alj and his team set forth on this trailblazing path, they acknowledge the challenge they face. “We are pursuing such strategies, and only time and resources are in our way to make further progress," the researchers concluded. Nonetheless, the promise of a future where triple-negative breast cancer patients could potentially have more effective treatment options is an inspiring prospect, underscoring the power of innovation and relentless scientific pursuit in the battle against cancer.

Signs and symptoms of breast cancer may include:

If you find a lump or other change in your breast — even if a recent mammogram was normal — make an appointment with your doctor for prompt evaluation.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

Like these kind of feel good stories? Get the Brighter Side of News' newsletter.