Eradicating stem cells in breast cancer

Results from a small clinical trial of 45 patients with locally advanced breast cancer suggests that the novel agent lapatinib (Tykerb, GlaxoSmithKline) has an effect on tumour-causing breast cancer stem cells. Lapatinib is approved to treat breast cancer that has metastasized and contains the protein marker called HER-2 in the US, but not the EU.

Chemotherapy can remove breast cancer tumours, but it often fails to root out the stem cells that can revive the cancer.

Comparing the challenge to eradicating stubborn weeds from a garden, the researchers at Baylor in Houston, Texas, said chemotherapy often fails because it leaves behind many of the stem cells that lead to recurrence.

Think of it this way: it's not enough to kill the dandelion blossom and stalk that appear above ground; you have to kill the root beneath the soil as well. The finding underscores the need to develop a treatment that can target stem cells in addition to the tumour itself. It appears that these cells, by their nature, are often resistant to the effects of anti-cancer drugs.

A cocktail of chemotherapy, together with the drug lapatinib, appears to kill both the tumour and the stem cells (6th European Breast Cancer Conference (EBCC): Abstract 204).

The Baylor researchers took biopsies from tumours of the patients with, and without, the HER-2 marker before and after different treatments. In the group of people whose tumours did not carry the HER-2 marker, the 31 patients received conventional chemotherapy. While the number of tumors significantly decreased, the proportion of cancer stem cells was greater than before the treatment.

The other group were given lapatinib and two common breast cancer chemotherapy drugs. That group saw a dramatic drop in tumour cells, and the percentage of cancer stem cells remained unchanged or even dropped slightly, but the tumour shrank dramatically. In contrast to treatment with conventional chemotherapy, the relative proportion of stem cells did not go up. The stem cells were, therefore, killed off with the same frequency as the bulk of the tumour.

This is the first time this has been demonstrated and offers an insight to developing new treatment strategies for fighting cancer in the future.

Source: Journal of Nat Cancer Institute

Genetic mutations and lung cancer - new developments in oncology

New results on genetic techniques that are helping doctors diagnose and treat lung cancer were released today at the 1st European Lung Cancer Conference jointly organized by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC) in Geneva, Switzerland.

In one report (Abstract No. 81O; 25th April), Israeli researchers from Rosetta Genomics, a biotechnology company developing microRNA-based technologies for diagnostic and therapeutic applications, described a test that may help make crucial distinctions between types of lung cancer. They demonstrated that the method can accurately distinguish between squamous and non-squamous forms of non-small-cell lung cancer, based on the levels of different microRNA molecules found in tissue samples.

MicroRNAs are short RNA molecules that regulate many cancer-related processes. Recently, the launch of new targeted therapies for non-squamous, non-small-cell lung cancer underlines the importance of accurate, objective diagnosis has taken center stage. The ability of physicians to accurately differentiate squamous from non-squamous NSCLC may be used as important treatment guide. For example, some treatments for non-squamous non-small-cell lung cancer can be deadly or ineffective in patients with the squamous form of the disease. Researchers expect the test to be approved for use during 2008.

In another report (Abstract No. 106PD; 25th April), Italian researchers showed that genetic analysis can help identify patients who are at high risk of relapse after surgery to remove lung cancer. The 3 gene signature may allow oncologists to classify patients with stage I non-small-cell lung cancer who underwent curative surgical resection in high or low risk molecular category, beyond conventional predictors and decide which appropriate treatments they should receive.

The test includes the gene LCK, which is an important marker of immune cell anticancer activity, DUSP-6 which regulates a signaling pathway involved in cancer spread, and ERCC1, which is thought to be a significant prognostic and therapeutic biomarker in non-small-cell lung cancer. These findings mean that we can potentially improve not only the prognostic stratification of patients, but also the choice of the more appropriate adjuvant drug after surgery, i.e. which patients will benefit most.


Source: ESMO

Magnets in cancer treatments - a new oncology tool or a bad idea?

Biopsy results can be ambiguous: sometimes they can be negative simply because there are too few malignant cells in the sample to be detected - not because all trace of disease has gone. Researchers from the University of New Mexico and the company Senior Scientific, both in Albuquerque, have devised a solution that harnesses the power of magnetic attraction.

The idea is to use magnetic iron oxide nanoparticles encased in a biocompatible material. These in turn can be coated with antibodies that bind to chemicals found only in cancerous cells. When injected into the body, thousands of the particles stick to cancer cells, turning them into miniature magnets. The cells can then be drawn towards magnets encased in the tip of a biopsy needle (Source: Physics in Medicine and Biology, vol 52, p 4009).

A mathematical model of the system confirmed that significant numbers of cancer cells, laden with nanoparticles, could be attracted to a needle within two or three minutes. In the lab, the researchers showed that a magnetised needle could attract leukemia cells surrounded by nanoparticles and suspended in blood or other synthetic materials designed to mimic bodily fluids. Nanoparticles have been used before to destroy diseased cells, but this was the first time they actually retrieved cells.

More recently, researchers have been wondering if cancer treatments be enhanced by something as simple as a magnet. A promising way to tackle some diseases is to deliver cells with modified genes to diseased tissue. Getting enough of the modified cells to the affected area can be tricky.

Claire Lewis and colleagues from the University of Sheffield inserted magnetic nanoparticles, as well as cancer-fighting genes, into monocytes, the white blood cells commonly used in gene therapy, and injected them into mice with tumours. A magnet placed above the tumour caused the cancer-fighting monocytes to congregate there (Source: Gene Therapy, DOI: 10.1038/gt.2008.57).

Metatasis in cancer - a new treatment strategy?

Metastasis is the spread of a tumour to different parts of the body and is a major driver of mortality in patients with advanced cancer.



Increasingly, researchers are discovering biomarkers that may predict early metastasis. For example, the chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. By studying the differential expression of CCR7 and CXCR4, along with the biomarker HER2-neu, is possible to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer.

As more biomarkers are identified in different cancer types, improved knowledge of this complex process may provide a platform for the development of molecularly targeted therapeutics aimed at either the tumor cell or its interaction with the host microenvironment.