When a woman is treated for breast cancer, one of the fears is that the disease may spread, or metastasize to other parts of the body. Even when diagnosed early and treated, with the patient showing no signs of disease, the cancer can re-appear five, 10 or even 15 years later. The site of these dormant cancer cells is most often the bone marrow. Scientists at Duke University have discovered how breast cancer cells migrate into the marrow and avoid detection, and described how the cells can be blocked from entering the bone and how they can be flushed out.
The findings by senior author Dorothy Sipkins and her team were published last week in Science Translational Medicine. Using real-time microscopy techniques, they tracked the migration of breast cancer cells through the bone marrow of mice, and identified two proteins: E-selectin enables the cancer cells to enter the bone marrow; while CXCR4 anchors the malignant cells to the bone and allows them to avoid detection.
The researchers used cells that were hormone-receptor positive – the most common type of breast cancer – which grow by exploiting the body’s oestrogen and progesterone. According to Sipkins (seen at left), “Biopsies of bone marrow have shown that even at very early stages of the disease, roaming cancer cells, or micrometastases, are making their way out of the breast and into the bone marrow. Now we know how they are getting in. Our findings could offer new strategies to intervene at the molecular level before dormant cells can take hold and cause relapse.”
One strategy explored by the scientists was to find a way to inhibit E-selectin and this was accomplished using a drug called GMI-1271 that’s currently being tested in human clinical trials. The compound was successful in preventing the breast cancer cells from entering and hiding in the bone marrow of mice.
Because it has been shown that microscopic metastases are able to spread to the bone marrow before a patient is even diagnosed with breast cancer, the researchers tested a strategy to flush the dormant cancer cells out of their hiding places in the bone marrow. This was successfully demonstrated using plerixafor, a drug normally used in bone marrow donors to force stem cells into the bloodstream prior to harvesting. Sipkins concluded: “We are hopeful that by understanding how these breast cancer cells migrate through the body and what their life cycle is, we can discover ways to make them more vulnerable and treatable.” Encouraging words, indeed.
Breast cancer never recurs. It was there all the time. Sometimes it only declares itself up to 20 years later in marrow, scar, nodes. Our ignorance about this is profound. That occult micro-metastatic disease can be specifically targeted is very promising. Our current approach is a chemotherapy blunderbuss called “adjuvant chemotherapy” for all invasive breast cancer.
David,
Your comments above are very interesting. “That occult micro-metastatic disease can be specifically targeted is very promising”. This is indeed scary. The words from a doctor” You are cured,”may come back to haunt him! Please read on!
LIFE SCIENCES
The Immunotherapy Dream Team
THE OPPORTUNITY
Despite a four-decade war against cancer and over $150 billion in research investment, five-year survival rates are virtually unchanged from 20 years ago in most types of cancer. In 2014, more than 1.6 million Americans were diagnosed, and close to 600,000 died from cancer. By 2030, cancer is expected to surpass heart disease to become the leading cause of death in the United States.
Immunotherapy is the only approach that has ever demonstrated an ability to generate durable remissions even in advanced tumors, but there are significant financial and organizational barriers to success. Immunotherapy-related research will receive less than 4% of the National Cancer Institute’s $4.9 billion cancer research budget in 2015, and the pharmaceutical industry’s R&D pipeline remains significantly focused on novel chemo and “targeted” agents.
THE PROGRAM
Through the support from Sean Parker, Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) formed an Immunology Research Dream Team dedicated to cancer immunology: “Immunologic Checkpoint Blockade and Adoptive Cell Transfer in Cancer Therapy.” The Immunotherapy Dream Team is focused on two approaches for this translational cancer research project, which will unite laboratory and clinical efforts towards the immunological treatment, control and prevention of cancer. The first is investigating blockades (by inhibitory molecules called “checkpoints”) of T lymphocytes’ inhibitory receptors, which block immune responses; and the use of antibodies to remove the checkpoints, once again allowing white blood cells called T lymphocytes to kill the cancer cells. Second, the Immunotherapy Dream Team is pursuing multiple adoptive cell transfer (ACT) approaches, which increase immunity.
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This sounds too good to be true! My only thought of caution is when “we” start tinkering with such a complicated system as the immune system, fools may rush in, where angels fear to tread! I have no doubts this is an excellent step in the right direction, but years of research will undoubtedly be necessary to make absolutely sure “we” do not inadvertently harm the patient. Just speak to a close friend of mine, who lost the love of his life, after taking “Embrel”.
Words of wisdom from an Octogenarian,
Ian
On the subject the subject of micro metastases, here is part of an article I sent you Kit. Brca1 and Brca 2. Sometimes forgotten, could there possibly be micro-metastases prior to the surgery? The premature removal of a woman`s ovaries, in itself is not without danger. Estrogen hormone replacement may be necessary , with possible serious problems. Reviewing this resource with her doctor will allow a woman to make a rational informed decision:
** http://www.cancer.gov/about-cancer/causesprevention/genetics/brca-fact-sheet
Sincerely,
Ian Grant-Whyte MA MD (Cambridge) L M C (Canada) A B F P (Ret)
**This text may be reproduced or reused freely. Please credit the National Cancer Institute .
PS. Many thanks to Harvard Radiology Professor ,Daniel Kopans, Professor Allison Kurian, Stanford University Medical School, and Bill Robinson, Office of Communications and public Liaison
It is appropriate for both men and women who have a family history that is suggestive of BRCA1 or BRCA2 to have genetic counseling for “possible testing”. Genetic counseling is an absolute must, and it is most important to have a genetic counselor to guide you from day one, up or down a very slippery slope.
There are basically three options:
(1) EarlyWatchful Waiting, with Mammography, MRI and a “thorough clinical examination”, periodically.
(2) Chemoprevention (Tamoxifen, Raloxifene), long term. All drugs can be associated with serious side effects.
(3) Prophylactic risk reducing surgery. Removal of remaining breast and ovaries. Here you are subjecting a woman to anesthesia, major surgery, all of which may have possible complications.
Thanks you David Dent and Ian Grant-Whyte for your thoughtful comments. It just struck me that the two of you have something in common: you both grew up in Durban in the 1940s; one of you (David) went on to become a surgeon, while the other (Ian) practised family medicine.