Thank you to Jennifer Texada at MD Anderson for bringing this great cancer treatment discovery to my attention….

(Image courtesy Introgen Therapeutics)

A gene therapy invented at The University of Texas M. D. Anderson Cancer Center is the first to succeed in a U.S. phase III clinical trial for cancer.  Introgen Therapeutics, Inc a spin out from MD Anderson, reported results of its phase III trial of Advexin, a modified adenovirus that expresses the tumor-suppressing gene p53, for end-stage head and neck cancer.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself.

“Cells become cancerous because p53 no longer functions. Restoring p53 works unlike any current cancer treatment because it treats the cancer genome,”said Jack Roth, M.D., professor in M. D. Anderson’s Department of Thoracic & Cardiovascular Surgery, who invented the drug and co-founded Introgen.

The trial showed that p53 expression in the patient’s tumor before treatment is a reliable biomarker for how to treat head and neck cancer. Patients with a favorable p53 profile who received Advexin had an average survival of just over 7 months, compared with just under 3 months for those whose tumor expressed high levels of mutant p53 before treatment. Patients with this unfavorable profile were better off taking the chemotherapy drug methotrexate, resulting in n average survival of just under 6 months.

“The important finding is that patients who benefit from treatment can be identified with the p53 biomarker. The biomarker will enable physicians to personalize treatment,” said Roth.

Better Quality of Life

Patients treated with Advexin experienced far fewer harmful side effects such as pneumonia than those who received methotrexate. The incidence of inflammation of the mouth lining and a decrease in white blood cells, for example, both dropped to zero for those receiving Advexin.

“That certainly results in a better quality of life,” Roth noted, which makes sense because p53 does not cause problems in normal cells.

Roth’s lab has been developing gene therapy for cancer since 1990. “We wanted to go beyond conventional treatment, because most of those treatments were not very effective,” Roth said. “Surgery and radiation are limited to the local tumor and once given, it’s very hard to repeat those therapies.  Chemotherapy inhibits DNA replication, but it also interferes with normal cells.”

Elaine Warburton  www.geneticsandhealth.com

I’ve known UK diagnostics company Lab-21 for some years now. My previous company Opaldia and Lab-21 effectively ‘grew up’ together. 

Amgen Limited UK and Lab21 have announced their partnership to introduce a new genetic therapy test for advanced bowel cancer treatment. Under the terms of the agreement, Lab21 will provide a screening test to indicate which patients are likely to benefit from Amgen’s new drug for advanced bowel cancer Vectibix® (panitumumab).

It is the first time that the European Commission (EU) has licensed a bowel cancer product with the stipulation that a predictive test should be carried out.  This is the start of companion diagnostics. The term companion diagnostic tests is used to describe diagnostic or prognostic tools that are specifically related to a therapeutic agent.

So I’m really pleased to see them link up with a visionary oncologist I’ve worked with for years - Dr Maurice Slevin at his London Oncology Clinic to introduce DXS’s KRAS pharmocogenetic test for advanced bowel cancer sufferers.

The KRAS gene is located on the short (p) arm of chromosome 12 at position 12.1.

 Source: NIH

Amgen scientists had discovered that only those patients with the non-mutated (wild type) KRAS would respond to Vectibix. Patients with metastatic bowel cancer will be tested for the presence of the wild type KRAS gene before they are prescribed the drug.

“It is particularly useful that Vectibix is being launched with a screening test for KRAS, which will help clinicians to target those patients most likely to benefit,”said Dr Maurice Slevin, “This means that patients unlikely to benefit will not receive a treatment which could expose them to unnecessary side-effects. Targeting cancer treatments is critical for the future if society is going to afford the ever increasing cost of innovative drugs.”

Approximately 60 per cent of patients with advanced bowel cancer have wild type KRAS. Of these, up to 60 per cent would be expected to respond to Vectibix.

Elaine Warburton  www.geneticsandhealth.com

Some patients, particularly young children, may be born with a genetic mutation which means they are at risk of hearing loss after taken antibiotics called aminoglycosides.  There is now a drive to consider screening patients for the genetic mutation known as m.1555A-G which is held in around 1 in 1,611 newborns in the USA, 1 in 206 newborns in New Zealand and 1 in 40,000 newborns in the UK.

Aminoglycosides are valuable antibiotics used for serious infections such as complicated urinary tract infections, TB and septicemia.  They are known to potentially cause damage to the ear - otoxicity. Individuals holding the mutation have an inherited predisposition which makes them extremely sensitive to the effects - they can end up with severe and permanent hearing loss.

It is estimated to cost US$122,000 for every child who becomes deaf plus another US$36,000 in educational costs. US estimates have placed the lifetime cost to society for a child who loses their hearing before language development at US$1 million.

The cost of this simple test to ascertain whether a person holds the gene  -  US $70!

Elaine Warburton