Knowing the Neighborhood
Treating breast cancer isn鈥檛 just about battling 鈥渂ad鈥� cells. Part of the challenge is understanding how the 鈥渉ome鈥� that cancer cells make can affect the course of the illness. Each patient, each tumor, is different. Mikala Egeblad鈥檚 lab at CSHL uses advanced imaging technologies to watch tumors interact with neighboring healthy cells (and drug-treated cells) in real-time.
In time-lapse microscopy, myeloid cells (green) are shown infiltrating an area of massive cell death (red) in a mouse treated with the anti-cancer drug doxorubicin.
Egeblad鈥檚 work shows us that even 鈥済ood鈥� cells can help cancers grow鈥攖heir neighborly instincts working against the patient. It鈥檚 this attention to all the players in a cancer cell鈥檚 world that is leading to improved and precise treatment options.聽Of course, it鈥檚 not just a cell鈥檚 neighbors that doctors need to worry about. CSHL President Bruce Stillman鈥攚ho directs the CSHL Cancer Center鈥攕pecializes in understanding how cells copy their genetic material. His lab recently has found that from the body can promote cell division in breast cancer cells, causing rampant tumor growth. With their target acquired, the team Stillman鈥檚 lab is now working to better understand this unsavory relationship, hoping to pave the way for therapies to bring these deadly growth signals under control.
Camila dos Santos and her team share a passion for knowing every inch of the battleground鈥攖he complex tissues of the breast鈥攊n health and illness. They鈥檙e studying patterns of gene activity in healthy breast cells, and how they change after a first pregnancy. It turns out that a mother鈥檚 genes and breast cells remember pregnancy, and this appears to increase future breast cancer susceptibility. Armed with knowledge stemming from this research, doctors may one day be able to block the cancer process from getting started in the first place.
Detect and聽Analyze
Cancer is adept at the art of invasion. But if we can access its battle plans, then we can craft counterattacks that are equally sneaky. Alexander Krasnitz and colleagues are key members of CSHL鈥檚 breast cancer counterintelligence team. They鈥檙e the codebreakers, using mathematical methods to identify and analyze clues hidden in billions of letters of genetic code about the mutations that drive individual breast cancers.聽With new technology that allows scientists to sequence the genome of a single tumor cell, Michael Wigler, Krasnitz, and others at the Lab can track the evolution of a cancer, to help predict its course and to know how to assemble forces to attack its specific vulnerabilities.
Eavesdropping on cells as they make proteins can also help researchers know if a cancer will develop. That鈥檚 what one team working with CSHL鈥檚 Adrian Krainer has done. Cells routinely edit the coded messages copied from genes in a process called RNA splicing. These edited messages direct the production of proteins鈥攚hich are the basis of most cell activities and structures. Sometimes, cells don鈥檛 get it right. Their messages are spliced abnormally. This can lead to the overproduction of proteins that promote cancer. Novel therapies to correct splicing errors are in the offing.
Halt and Treat
Breast cancer isn鈥檛 necessarily confined to the breast. Certain kinds of malignant tumors, called metastatic tumors, shed cells into the body鈥檚 blood vessels, enabling them to travel far and wide. Sometimes these deadly hitchhikers set up camp in new sites, for instance in the lungs. Aggressive expansion calls for aggressive treatment, but without access to tests that are effective at an early stage, it鈥檚 hard to catch tumors before they spread.聽Michael Wigler and his team are tackling the problem of detecting cancers before they spread鈥攚hen they are most treatable. They鈥檙e developing a 鈥渓iquid biopsy.鈥� It would involve a simple blood test to determine whether cancer cells are being shed from a primary cancer, and at what intensity. Highly sensitive technology makes it possible to detect subtle genetic changes by sampling cancer cells snagged from the blood. By tracking genetic changes, doctors can predict a cancer鈥檚 course and tailor treatments to specific cancer subtypes鈥攁 potential life saver.
David Spector, CSHL鈥檚 Director of Research, is also working on ways to prevent metastasis. Investigating the wanderlust of cancer cells, his lab has recently identified RNA molecules whose loss can inhibit the migration of cancer cells from breast to lung. With their target acquired, the lab鈥檚 work could inspire new precision treatment options.
But even precision treatments are not enough. Doctors and patients have learned that the most precise cancer drugs we possess usually stop working after a time鈥攐ften just a year or two. The drug Herceptin, for instance, can work wonders for patients with a certain type of breast cancer, yet relapses are common.聽Nicholas Tonks, a biochemist at CSHL, is working with his team on a completely new way of possibly preventing relapse in such cases. Encouraged by studies in mice that suggest a drug Tonks developed blocks a driver of metastasis, the team is about to join forces with clinicians at North Shore-LIJ Medical Center in clinical trials.