On October 21, 2025, two landmark advances in women’s cancer research emerged from opposite ends of the United States, each promising to change the way clinicians and scientists approach some of the most stubborn challenges in breast and ovarian cancer. At Cold Spring Harbor Laboratory (CSHL) in New York, a team led by Associate Professor Camila dos Santos revealed a breakthrough in overcoming hormone therapy resistance in estrogen receptor-positive (ER+) breast cancer—a subtype that accounts for roughly 75% of breast cancer cases worldwide. Meanwhile, in the heartland of South Dakota, Dr. Pilar de la Puente at Sanford Research celebrated a prestigious seven-year MERIT Award from the National Institutes of Health to fuel her innovative work on ovarian cancer chemoresistance and the tumor microenvironment.
These two stories, though unfolding in different labs and focusing on distinct cancer types, share a common thread: a commitment to unraveling the complex biological and environmental factors that allow women’s cancers to evade treatment, recur, and metastasize. Together, they offer new hope for patients, clinicians, and families who have long sought more durable solutions in the fight against these diseases.
For decades, ER+ breast cancer has been treated with hormone therapies like tamoxifen, which block the estrogen signals that drive tumor growth. Yet as reported by CSHL, resistance to these therapies remains a formidable obstacle. Tumors often adapt, finding new ways to grow despite the drugs, leading to recurrence and, all too often, metastatic spread. According to the original research published in Nature Communications (DOI: 10.1038/s41467-025-64255-8), the dos Santos lab has now identified a key player in this process: the protein BPTF, or Bromodomain PHD Finger Transcription Factor.
BPTF, previously considered a secondary actor in breast cancer biology, regulates the architecture of chromatin—the tightly packed DNA-protein complex that controls gene expression. Earlier studies had shown that knocking out BPTF could slow tumor growth, but it didn’t stop tumors from forming, leading some in the pharmaceutical world to lose interest. But dos Santos and her team took a fresh approach. By crossbreeding established mouse models of ER+ breast cancer with BPTF knockout strains, they found something remarkable: the resulting tumors maintained their dependence on estrogen signaling throughout progression, never shifting toward hormone independence—a common resistance pathway in conventional models.
This consistency allowed the researchers to test the effects of tamoxifen on BPTF-deficient tumors. The results were striking. Tumors lacking BPTF remained highly sensitive to hormone therapy, exhibiting significant and sustained responses to the drug. Further experiments using organoid cultures, human breast cancer cell lines, and genetically engineered mouse models confirmed that removing BPTF could restore hormone sensitivity even in previously resistant tumors. As the CSHL team put it, targeting BPTF could "reprogram" resistant cancer cells back into a hormone-dependent state, giving current therapies a renewed edge and potentially delaying recurrence and metastasis.
"Deciphering tumor heterogeneity, growth patterns, and metastatic behaviors was critical to uncovering these insights," said graduate student Dhivyaa Anandan, underscoring the importance of detailed, mechanistic research over simplistic models. Mechanistically, the study suggests that BPTF’s role in chromatin remodeling enables tumor cells to rewire their signaling pathways and evade therapy. Disabling BPTF disrupts these adaptive programs, keeping tumors vulnerable to hormone blockade.
The clinical implications are profound. As hormone therapies currently provide only temporary reprieve for many patients, BPTF inhibitors could be developed as adjuvant treatments, maintaining therapy sensitivity and preventing the emergence of metastatic disease. With ER+ breast cancer representing such a large proportion of cases—and with so many patients facing relapse—this discovery opens a promising new therapeutic horizon. As the dos Santos lab’s findings ripple through the research community, attention is already turning to the development of drugs targeting BPTF and related chromatin remodelers, which have historically been overlooked in cancer therapy.
While CSHL’s work focuses on the genetic and epigenetic underpinnings of breast cancer resistance, Dr. Pilar de la Puente’s research at Sanford Research in Sioux Falls, South Dakota, tackles a different but equally daunting foe: the stubborn recurrence of ovarian cancer after chemotherapy. Dr. de la Puente, a biomedical engineer and cancer biologist originally from León, Spain, was recently awarded a 7-year MERIT Award from the NIH—an honor reserved for the top one to two percent of scientists in their field, and one that cannot even be applied for. The grant, worth nearly $4 million, will support her lab’s efforts to understand and disrupt the tumor microenvironment’s role in cancer resistance.
"What we have learned in the lab is that it is very important to understand not only the cancer cells and how they work but also the environment they are in," Dr. de la Puente explained, as quoted in Sanford Health News. She likens cancer to a seed and the surrounding tissue—the tumor microenvironment—to the soil. Chemotherapy, she notes, affects both the seed and the soil. However, while it kills cancer cells, it can also alter the environment in ways that promote resistance when the cancer returns. Her lab is searching for ways to block these environmental changes and make chemotherapy more effective for longer periods.
Dr. de la Puente’s work doesn’t stop at chemoresistance. Her team is also hunting for early biomarkers of ovarian cancer, which is notoriously difficult to diagnose in its early stages because symptoms—like bloating and fatigue—are so common and nonspecific. "If ovarian cancer is caught in Stage 1, the survival rate is 90 percent," she emphasizes. By identifying reliable biomarkers, her research could transform survival statistics by catching the disease when it is most treatable.
Another front in her lab’s battle involves immunotherapy, which has revolutionized treatment for some cancers but has largely failed in breast and ovarian tumors. By studying why these cancers are immunologically "cold"—lacking the immune cells needed to respond to therapy—her team hopes to find ways to make them "hot," or more visible to the immune system. Finally, using microfluidics, Dr. de la Puente investigates how and why cancer cells metastasize to specific sites in the body, a question that could reveal new targets for preventing deadly spread.
Dr. de la Puente’s journey from Spain to South Dakota reflects her passion for building and problem-solving. Her engineering background gives her a unique perspective on cancer biology, one that has garnered national recognition and placed Sanford Research on the map for women’s cancer research. As she puts it, "It has happened that I have been able to get great success here in this place that fewer people know about." Her commitment extends beyond the lab, as she mentors young scientists and advocates for greater representation of contemporary women in science, even starring in a comic book distributed in schools across two continents.
Both the CSHL and Sanford Research breakthroughs highlight the critical importance of looking beyond the obvious—whether it’s the genetic switches that let breast tumors outsmart therapy or the supportive environment that shelters ovarian cancer from chemotherapy. As new drugs and diagnostics move from bench to bedside, these discoveries promise to tip the scales in favor of patients, offering not just hope, but a roadmap to better, longer-lasting outcomes. For researchers like dos Santos and de la Puente, and the patients whose lives they hope to change, that future can’t come soon enough.
