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Genetically modified purple tomatoes, anti-oxidants and cancer

By on October 28, 2008

Tomatoes genetically modified
to be rich in antioxidants called anthocyanins appeared to extend the life
spans of cancer-prone mice, according to a study reported via letter in Nature Biotechnology.

Purple Toms
The modified tomatoes were created by adding two genes (Delila and
Rosea1) from the snapdragon flower. The anthocyanins, which belong to the
flavonoid class of antioxidants, gave the tomatoes a peculiar purple
colour.

The two genes that were isolated are responsible for flower pigmentation
and, when introduced in other plants, turned out to be the perfect
combination to produce anthocyanins, the same phytochemical found in
blueberries.  Anthocyanin is thought to have anti-cancer properties.

Chemical tests revealed that the purple tomato has a very high
antioxidant activity, almost tripled in comparison to the natural fruit,
making it very useful to study the effect of anthocyanins.

The researchers fed a powder obtained from the purple tomatoes to mice
that lacked the p53 gene, which helps protect against cancer. These mice
had an average life span of 182 days compared to 142 days for
p53-deficient mice fed a standard diet.

The significance of these findings?

According to one of the researchers quoted by the BBC:

"Most people do not eat five portions of fruits and vegetables a day,
but they can get more benefit from those they do eat if common fruit
and veg can be developed that are higher in bioactive compounds."

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Overcoming resistance to treatment with EGFR inhibitors

By on October 28, 2008

In a preclinical study presented at the EORTC-NCI-AACR meeting, a compound known as XL184 (Exelixis),  showed
encouraging results in boosting sensitivity to erlotinib (Tarceva) and gefitinib
(Iressa) in drug-resistant lung cancer. 

Gefitinib and erlotinib belong to a
class of targeted drugs that target the epidermal growth factor
receptor (EGFR) gene, which is mutated in many non-small cell lung
cancers (NSCLC). 

MET kinase, which is inhibited by XL184, is implicated in the
resistance to EGFR kinase inhibitors. This approach potentially has the opportunity to turn the resistance mechanisms off, thereby allowing Tarceva to work more effectively in NSCLC when taken in combination with a MET kinase inhibitor such as XL184.

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Exelixis XL184 has early activity in medullary thyroid cancer

By on October 28, 2008

Medullary thyroid cancer is difficult to treat, but recent results with a compound known as XL184 have shown some early and encouraging responses.  They were reported at the EORTC-NCI-AACR meeting in Geneva last week.  XL184 (Exelixis), targets cell growth and migration, as well as blood vessel growth (angiogenesis), through inhibition of MET kinase, VEGFR and RET kinase.

In a phase I study, 84 patients with a variety of advanced tumours that were not amenable to standard therapy were administered XL184 for either the first five days of a 14-day cycle or daily throughout the cycle. The group included 36 patients with advanced medullary thyroid cancer, for which no treatment is known to work.  Response to the drug was assessed at 28 days and subsequently every eight weeks. 

The impact on tumour shrinkage was noticeable in the medullary thyroid cancer patients, where the overall disease control rate (ie the percentage of patients with either a partial response to the drug or prolonged stable disease for more than three months) was an amazing 84% in the 25 patients who have been followed for at least three months.

In addition, partial response, where tumours shrink by at least 30%, was achieved in 55% of the 22 patients with measurable disease who have been followed for at least three months. Most of the others experienced prolonged stable disease beyond three months, and for most of these patients there was actually tumour shrinkage.

Three of the medullary thyroid cancer patients had unmeasurable disease. Tumour biomarkers such as plasma calcitonin and CEA dropped significantly after therapy in most of the patients.

Of the 84 patients, including patients with diverse cancers, disease stabilisation for at least three months was seen in 28 cases. In 16 of those cases, the disease was stable for six months or more, the study found. The most common adverse effects of the drug included diarrhea (24%), nausea (18%) and fatigue (15%). 

These results have put the drug’s development on a fast track,
prompting the accelerated initiation of a large phase III trial.

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