• Turning Point 2013

    Learning from Tissue

    Most research into the underlying mechanisms of cancer entail tissue samples, and women's cancers are no exception.

    Ronny Drapkin, MD, PhDRonny Drapkin, MD, PhD 

    For nearly a decade, pathologists have been gathering evidence that high-grade serous ovarian cancer (HGSOC) was a fallopian tube malignancy masquerading as an ovarian one, but the evidence was circumstantial. In 2011, a team led by Ronny Drapkin, MD, PhD, an anatomic research pathologist at Dana-Farber's Center for Molecular Oncology Pathology and co-director of the TRR, developed the means to study cells lining the fallopian tube (the fallopian epithelium) by culturing them in the laboratory. His team's work was based on molecular studies by Christopher Crum, MD, director of GYN Pathology at DF/BWCC, proving that at least some high-grade ovarian cancers do originate in the fallopian tube.

    Using tissue from women who had their fallopian tubes removed for reasons unrelated to cancer, the researchers also established a model that mirrors the structure and function of normal fallopian tube tissue in the body, enabling them to study how this tissue responds to physiological stressors that can trigger cancer development.

    "We made a lab-based platform to study the cell of origin in fallopian tube tumors," says Dr. Drapkin. "This was all dependent on living tissue [from human donors]." The findings allow clinicians and scientists to identify different types of HGSOC, and possibly discover biomarkers that signal the presence of the disease and test potential therapies.

    Kornelia Polyak, MD, PhDKornelia Polyak, MD, PhD 

    In her lab, Dana-Farber breast cancer geneticist Kornelia Polyak, MD, PhD, uses human breast tissue samples to study groups of cells within tumors and monitor how they change and respond to treatment. This so-called tumor heterogeneity reveals that one tumor can have different subtypes of cells, with different genes and proteins and varying rates of growth. For this reason, treatments may need to be combined to destroy different cancer cell types.

    Using sophisticated technology, Dr. Polyak compares tumor samples taken before and after treatment to determine how their genetic makeup (genotype) and physical characteristics (phenotype) have changed. Physical and genetic differences among cancer cells, she says, may influence how fast tumors spread or how quickly they become resistant to therapy.

    "Animal and cell culture models are good for some research," says Dr. Polyak. "But models may not faithfully reflect reality. We have to study human tissue and listen to what it tells us. Models show what can happen, but human tissue shows what really does happen."

    Dr. Polyak is also collaborating with Nancy Lin, MD, clinical director of the Breast Oncology Center, on a clinical trial that is heavily dependent on using tissue samples to answer key questions about treatment effectiveness.

    The most successful drug treatments for breast cancer target estrogen receptors, progesterone receptors, or HER2 receptors on cancer cells. Unfortunately, many women have what is called triple-negative breast cancer, meaning that they lack all these receptors. This type of breast cancer is often driven into remission by standard chemotherapy, but patients whose triple-negative tumors do not go away after chemotherapy may have a poor prognosis.

    Judy Garber, MD, MPHJudy Garber, MD, MPH 

    Two recent clinical trials led by Judy Garber, MD, MPH, tested the use of the chemotherapy drug cisplatin in patients with triple-negative breast cancer. Dr. Garber collaborated with molecular pathologist Andrea Richardson, MD; Daniel Silver, MD, PhD; Eric Winer, MD; and their teams. They analyzed tumor tissue collected before and after cisplatin treatment, and looked for features in cancer cells' DNA that predicted a favorable response to the drug.

    The analyses made it possible to predict which patients were most likely to respond to cisplatin treatment. "That way, we could give cisplatin to patients with the marker, who are more likely to respond to it," says Dr. Garber. "For those without the marker, we would not waste time with cisplatin and instead try something else."

    Technology has given scientists the ability to discover many of the anomalies in cancer cells' genetic programming and the capacity to target those glitches to stop the cancer or, at least, slow its progression. "Living" tissue is now an essential resource for scientists studying women's cancers. It lies at the heart of such breakthroughs.

    "Without tissue, cancer research would go much more slowly," says Dr. Garber. "Now, we can sequence the entire genome of a tumor to find its Achilles' heel. Much of the progress we've made is because we can study the patient and her tumor through tissue. That gives us an edge over other types of medical research."

    Turning Point 2013 Table of Contents 

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