By Michael Price
ScienceNOW Daily News
28 August 2008

Why do some cancers relapse years after treatment? The question has frustrated scientists and doctors for decades, but a new study of lab mice suggests an answer: Cells may break off from a tumor even before they become cancerous, seeding the body with cells that evade detection and lie dormant for years before turning into tumors of their own.Researchers already know that cells can break off from a malignant tumor and cause cancer elsewhere in the body, a process known as metastasis.

Some tumor cells that travel to distant sites in the body and lay dormant for long periods require help from factors in their immediate environment to eventually develop into metastases, researchers reported in the August 1 Cancer Research. This conversion from hibernation to active growth, they found, is initiated by a reorganization of the dormant cells’ interior cytoskeletal architecture, induced by signaling molecules immediately outside the cell in the extracellular matrix (ECM), and could be disrupted by targeting a molecular pathway that regulates the cytoskeleton.

Led by Dr. Dalit Barkan from NCI ’s Laboratory of Cancer Biology and Genetics, the study used mouse models and a three-dimensional (3-D) culture system, in which signaling factors typically found in the tumor microenvironment could be introduced.

Breast Cancer Research and Treatment Vol. 110/Number 3/ August 2008

Abstract  We retrospectively evaluated whether a surgical strategy benefits patients with operable lung metastasis of breast cancer. Between 1960 and 2000, 90 patients (mean age 55.1; range 32–77) with lung metastasis (79 solitary, 11 multiple) underwent surgery as follows: wedge resection (n = 10), segmental resection (n = 11), lobectomy (n = 68) and pneumonectomy (n = 1). The metastases were completely resected in 89% of them. One patient died due to surgical complications. The overall 5- and 10-year cumulative overall survival rates were 54% and 40%, respectively (median, 6.3 years). Fifteen patients survived without relapse for over 10 years. They were 24% of those who progressed for 10 years or more after lung surgery. The most significant prognostic factor was disease-free interval (DFI) and stage at breast surgery. The 10-year survival rates of those with ≧3 and <3 years of DFI were 47% and 26%, respectively (P = 0.014). Survival times were significantly longer for patients with clinical stage I at breast surgery than those with stage II–IV (P = 0.013). Our data, although limited and highly selective, suggest that surgical approach to lung metastasis from breast cancer may prolong survival in certain subgroups of patients to a greater extent than systemic chemotherapy alone. Surgical approach to lung metastasis of breast cancer, if possible, should be a treatment of choice to a great extent.

CHICAGO, June 2 — Combining targeted biologic therapies after progression of metastatic HER2-positive breast cancer may improve response despite prior treatment with multiple trastuzumab (Herceptin) regimens.

Addition of the tyrosine kinase inhibitor lapatinib (Tykerb) to the monoclonal antibody trastuzumab reduced risk of disease progression 27% compared with lapatinib alone, reported Joyce O’Shaughnessy, M.D., of the Baylor-Sammons Cancer Center in Dallas, and colleagues here at the American Society of Clinical Oncology meeting.

Continued use of trastuzumab after recurrence or progression is common in practice, but the study provides some of the first supportive clinical data for the practice, commented Francisco J. Esteva, M.D., Ph.D., of the M.D. Anderson Cancer Center in Houston, who was a discussant for the study.

“Total HER2 blockade with lapatinib and trastuzumab may provide a chemotherapy-free option for HER2-positive metastatic breast cancer patients,” Dr. O’Shaughnessy said.

ScienceDaily (Aug. 12, 2008) — Precisely targeted radiation therapy can eradicate all evidence of disease in selected patients with cancer that has spread to only a few sites, suggests the first published report from an ongoing clinical trial.

In the August 15, 2008, issue of Clinical Cancer Research, (published online August 12) researchers from the University of Chicago Medical Center report that targeted radiation therapy had completely controlled all signs of cancer in 21 percent of patients who had five or fewer sites of metastatic disease

Scientists using a three-dimensional cell culture system have identified a mechanism by which dormant, metastatic tumor cells can begin growing again after long periods of inactivity. The new findings indicate that the switch from dormancy to proliferative, metastatic growth may be regulated, in part, through signaling from the surrounding microenvironment, which leads to changes in the skeletal architecture of dormant tumor cells. Targeting this mechanism may also provide strategies for inhibiting the switch from dormancy to proliferation. The results of this study by National Cancer Institute (NCI) scientists and their collaborators, appears in the August 1, 2008, issue of Cancer Research. NCI is part of the National Institutes of Health.

Scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have made a key discovery about the mechanism of breast cancer metastasis, the process by which cancer spreads. Focusing on a gene dubbed “Dachshund,” or DACH1, they are beginning to pinpoint new therapeutic targets to halt the spread of cancer