October is National Breast Cancer Awareness Month, and people across the world are helping raise awareness and support through runs, walks, events – and, at the Weizmann Institute of Science, through research.
Before breakthroughs in breast cancer research ever appear in the news or on the market, there are cadres of scientists working tirelessly to discover new ways to prevent, diagnose, and treat this all-too-common disease. Here are some of our advances over just the past year:
A chain reaction leads to cancer – and perhaps personalized treatments. A team that includes Weizmann’s legendary cancer researcher Prof. Moshe Oren made a breakthrough while studying the “hippo pathway”: a chain of biochemical reactions that, when disrupted, can cause fruit flies to grow so large that they resemble the giant mud-basking mammals. In humans, however, this disruption can cause cancer. Two hippo-related genes, LATS1 and LATS2, appear at lower-than-normal levels in many breast cancer tumors, leading the scientists to investigate exactly how low LATS levels lead to breast cancer.
One of their major findings was that LATS1 and 2 play different roles in protecting us against breast cancer, and it is hoped that further studies will allow clinicians to factor in these roles when selecting a patient’s therapy – for example, identifying patients who will likely benefit from hormone therapy and sparing unnecessary treatment for those who may not. Furthermore, the team’s discovery that tumors with reduced LATS2 activity are critically dependent on glucose may help develop new breast cancer treatment options.
A partnership for personalized breast cancer treatment. In a promising, ongoing study, clinicians and researchers from Sheba Medical Center and Tel Aviv University partnered with Weizmann’s Nancy and Stephen Grand Israel National Center for Personalized Medicine (G-INCPM) to identify strategies for individualized treatment for breast cancer patients, based on the variety of gene expression patterns that underlie tumor progression and response to therapy. The G-INCPM is an on-campus resource for all of Israel’s biomedical researchers, allowing them to collaborate on the research needed to create new drugs and therapeutic approaches for a whole host of diseases.
Tracking 33 women being treated for breast cancer, Sheba clinicians collected three types of tissue samples from each patient: a tumor biopsy at time of diagnosis, a sample of the surgically removed tumor, and a sample of non-cancerous tissue adjacent to the tumor site. These samples are undergoing a full proteomic analysis at Tel Aviv University, after which G-INCPM experts will analyze the data and connect gene patterns with specific clinical outcomes. This multi-platform project is expected to help develop new tools for diagnosing cancer, as well as identify genetic profiles associated with breast cancer’s resistance to particular types of treatment.
Designing a personalized cocktail to prevent cancer regrowth. Our Israel Prize-winning Prof. Yosef Yarden has long studied EGFR: a growth-factor receptor that, when mutated, promotes cancer. Pharmaceutical compounds called TKIs are prescribed for patients whose tumors have an EGFR mutation – however, while TKIs can shrink tumors, new mutations appear within a year that cause the cancer to recur. Looking for a way to prevent such recurrence, Prof. Yarden and his team turned to a selection of existing cancer drugs known to block EGFRs.
The scientists examined tumor response (lung cancer, in this experiment) to a combination of three already-approved therapies: cetuximab, trastuzumab, and the TKI inhibitor osimertinib. They found that, when administered together, the three compounds provide effective, long-lasting treatment and thwart tumor regrowth. The results show that this drug combination simultaneously blockades several drug resistance mechanisms.
One of the study’s most exciting aspects is that one of the drugs used, trastuzumab, targets the receptor characteristic of HER2-positive breast cancer, which is particularly aggressive and hard to treat. This indicates that the combined-drug approach could prove applicable to HER2-positive breast cancer, as well as lung and other malignancies. The scientists’ findings will form the basis of clinical trials in human cancer patients.
