Research roundup: Overcoming EGFR-targeted therapy resistance in breast cancer, and more

Femtech World explores the latest developments in women’s health research – from overcoming EGFR-targeted therapy resistance in breast cancer to understanding obesity’s role in triple-negative breast cancer, and more.

EGFR-targeted therapy resistance in breast cancer

Researchers have reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers.

The article explores how cancer cells evade these treatments by activating alternative survival pathways and offers an in-depth look at the molecular barriers to EGFR inhibition, providing insights that could inform the development of more effective and durable treatments.

EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge.

In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumour growth despite therapy.

The review describes how tumour cells in these cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked.

By analysing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways.

Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes.

Several clinical trials are evaluating these approaches in patients.

For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer.

These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumours.

The review also emphasises the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies.

Screening women with diabetes for intent to conceive at every doctor visit

Adverse pregnancy outcomes such as miscarriages or birth defects are common in individuals with pre-existing diabetes and are often related to modifiable factors such as maternal high blood sugar and body mass index (BMI).

With this in mind, a new, joint guideline released by the Endocrine Society and the European Society of Endocrinology (ESE) has recommended that women with diabetes receive proper preconception care.

This includes access to emerging diabetes technology and therapeutics to manage their blood sugar before, during and after pregnancy.

Screening women of reproductive age who have diabetes for intent to conceive at every reproductive, diabetes and primary care visit helps ensure they get the appropriate preconception care and reduces health risks.

Care suggestions from the guidelines include screening by asking all women with diabetes of reproductive age about intent to conceive at every reproductive, diabetes and primary care visit; timing delivery before 39 weeks for pregnant individuals with diabetes as the risks associated with continued pregnancy may outweigh those of early delivery; discontinuing anti-obesity medications called GLP-1s prior to pregnancy; and, avoiding prescribing metformin in pregnant individuals with preexisting diabetes already on insulin.

Further suggestions include using diabetes technology, recommending hybrid closed loop systems for pregnant individuals with type 1 diabetes; and suggesting that women with diabetes use contraception until they are ready to become pregnant.

Premenstrual symptoms linked to increased risk of cardiovascular disease

A new study has revealed that women diagnosed with premenstrual symptoms have a slightly increased risk of developing cardiovascular disease later in life.

Premenstrual symptoms include premenstrual syndrome (PMS) and the more severe form, premenstrual dysphoric disorder (PMDD).

The study followed more than 99,000 women with premenstrual symptoms for up to 22 years, comparing their health with women without these symptoms – both in the general population and by comparing them with their own sisters to take into account hereditary factors and upbringing.

The results show that women with premenstrual symptoms had about a 10 per cent higher risk of developing cardiovascular disease.

When the researchers also looked at different types of cardiovascular disease, they found that the link was particularly strong for heart rhythm disorders (arrhythmias), where the risk was 31 per cent higher, and for stroke caused by a blood clot, where the risk was 27 per cent higher.

Even after the researchers took into account other factors such as smoking, BMI and mental health, the link between premenstrual symptoms and increased disease risk remained.

Research has not yet identified the cause of this link, but the researchers behind the study suggest three possible explanations.

One is that women with premenstrual symptoms may have a disrupted regulation of the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure and fluid balance in the body, among other things.

The second is that these women have increased levels of inflammation in the body, which is a known risk factor for atherosclerosis and other heart problems.

Finally, it may be because women with premenstrual symptoms may have metabolic abnormalities, which are linked to an increased risk of both stroke and heart attack.

Obesity’s role in triple-negative breast cancer

Among the various subtypes of breast cancer, triple-negative breast cancer (TNBC) stands out due to its aggressive nature and poor prognosis.

It is characterised by the absence of three critical hormone receptors: oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, which are common targets for breast cancer therapies.

Consequently, TNBC lacks targeted treatment options, relying primarily on conventional cytotoxic therapies, often referred to as chemotherapy in which drugs kill or damage cancer cells.

This limitation contributes to the subtype’s high recurrence rates and significantly lower survival rates compared to other forms of breast cancer.

Researchers have now discovered that exosomes, messenger nanovesicles that carry proteins, RNA, and other molecules to other cells, that are released into the blood by different organs and tissues in obese, insulin-resistant models, carry signals that turn otherwise slow-moving TNBC cells into highly mobile, invasive cells.

This is the first time a study has shown that exosomes from an obese, diabetic environment directly cause this aggressive change in TNBC, and that Rho-proteins (molecular switches that turn “on” or turn “off” signal transduction pathways) play a key role in driving the change.

According to the researchers, by revealing how obesity-driven exosomes push aggressive breast cancer to spread, they hope to unlock new blood tests and drug targets, like Rho-protein inhibitors that stop this deadly process.

“These findings support the development of clinical tests to quantify obesity-derived exosomes in patient plasma as noninvasive biomarkers of metastatic risk, allowing earlier identification and tailored management of aggressive TNBC,” said corresponding author Gerald Denis, Shipley Prostate Cancer Research professor and professor of pharmacology, physiology and biophysics.

“Ultimately, our goal is to improve survival and quality of life for patients facing both metabolic disease and hard-to-treat cancers.”