Despite the exciting prospects of treating cancer patients with gene therapy techniques, many challenges remain, according to leading scientists.

Early this year, a study published in London-based magazine Nature indicated that inserting p53 genes into rats quickens the onset of ageing and weakens their general physical condition.

Although an adenovirus used as a vector to weaken and even kill cancerous cells has been found to produce limited side effects in humans, such as fever, some say the side effects may be serious for late-stage cancer patients.

Other scientists worry the virus vector could prompt the body's own antibodies to kill the virus itself and stop it from entering target cells.

More serious but untested worries include concern about the conveyed therapeutic gene, or other genes of the virus vector, may integrate with the human genome to lead to unexpected gene mutations causing cancers and other diseases.

Lu Youyong of the School of Oncology, Peking University, and a leading scientist behind Gendicine research, said the injection of the gene into tumour cells prevents the natural antibody reactions of the human body.

"As for the effect of the p53 gene in weakening the human body itself, we must balance this effect with the therapeutic role against cancer," Lu said. "Further studies might reveal a mechanism to eliminate the weakening effect of the p53 gene."

But the intra-tumour injection of the gene therapy medicine can hardly reach untested remote tumour cells. "Gene therapy itself cannot solve everything. It must work together with traditional operations, chemotherapy or radiotherapy to treat cancers," Zhang said.

Gu Jianren of the Shanghai Institute of Cancer, the prominent scientist who first introduced gene therapy to China, supports the advances of Gendicine and H101.

"The gene therapies are not a panacea for all cancers, not because they are ineffective, but because we have not learned enough of the mechanism of cancers and the mechanism of all gene mutation actions," Gu said.

He recommended that researchers try more therapeutic genes, use more vectors and attempt different approaches to develop gene therapies.

So far, more than 20 genes have been found to be related to the formation of tumour cells.

Fang Bingliang, an associate professor at the University of Texas MD Anderson Cancer Centre in the United States, has tried another approach to gene therapy.

According to Fang, in typical gene therapies, scientists deliver certain genes to human cells, or deliver oncolytic viruses to eliminate human cells containing certain genes that are dysfunctional. These approaches all involve the use of very big molecules or big molecule-based viruses as drugs, which cannot move everywhere in the human body. There is always the potential for antibody reaction.

Fang's method is identifying some small chemical molecules to curb the expression of certain genes. The advantage of this method is the drug can move around the body. "This combines the advantage of traditional chemical method, such as all-body dosage, low costs and no antibody reaction, and the novel gene studies. This might be the future direction of gene therapies," said Fang.

Source: China Daily