WASHINGTON _ Almost 25 years have passed since PresidentRichard Nixon signed landmark legislation making the eradication ofcancer a national priority yet researchers still are struggling in thetrenches of cancer research. Despite decades of impressive advancesin basic science and treatment strategies, cancer will be the leadingcause of death in the U.S. by the year 2000.

Approximately 40 percent of Americans will develop cancer and oneout of four will die from cancer. These hard facts have led somecritics to complain that the so-called war on cancer has been a losingone. It's also been an expensive one. Since 1971, the annual federalappropriation for the National Cancer Institute (NCI) has increasedfrom $200 million to more than $2.25 billion in 1996. Some of thatmoney has helped to fuel the extraordinary growth of thebiotechnology industry in the last decade.

But even with all the heavy spending and the proliferation of newcompanies and ideas, for many patients, cancer is still a deadlydisease. Because of the slow progress, Wall Street has lost some ofits enthusiasm to fund cancer-focused companies and Congress couldpare down the NCI's budget in coming years.

Despite the difficulties and disappointments inherent in battlingcancer, researchers are lobbying hard to maintain government andprivate funding for the effort. More than 7,000 scientists and industryrepresentatives gathered in the nation's capitol on Saturday to kickoff the five-day 87th annual meeting of the American Association forCancer Research (AACR).

"The prime force holding back advances in the field of cancerresearch will not be a lack of scientific ideas but a lack of funding,"warned James Holland, a professor in the department of neoplasticdiseases at the Mount Sinai School of Medicine, in New York. "Itwill be harder and harder to conduct clinical research in the futurebecause HMOs [health maintenance organizations] and insurancecompanies don't understand the need to invest in research andhaven't done so." Holland spoke to journalists at a press conferencecommemorating Nixon's 1971 National Cancer Act legislation. Somehighlights of the AACR meeting's first two days follow:

Gene Therapy Survives A Tough Year

1995 was a politically charged year for gene therapy. A NationalInstitutes of Health report pronounced it "over-hyped" and exhortedscientists to return to basic scientific research. However, gene therapyresearchers have not lost their infectious enthusiasm.

"There have been a lot of expectations for gene therapy and a lot ofhype," conceded gene researcher Inder Verma, of the La Jolla, Calif.-based Salk Institute. "It's unfair to criticize gene therapy so harshlywhen it's only been 12 years since we made the first vector. Everyoneagrees that this technology will have a huge impact on clinicalmedicine by the next century."

Verma has focused on using gene therapy to modify the biology ofthe immune system in cancer patients rather than on the moretraditional paradigm of replacing or repairing faulty genes. Accordingto Verma, the greatest challenge has been finding a vector that canefficiently deliver genes to specific cells and induce sustainedexpression. Experiments conducted by Verma and his associates havedemonstrated that a lentiviral vector was able to deliver genes to non-dividing cells in the brains of adult rats. That finding could beimportant for treating patients with cancerous tumors composed ofnon-dividing cells such as those found in the liver or brain.

Arthur Bank, professor of medicine and genetics at ColumbiaUniversity's College of Physicians and Surgeons, in New York,reported that gene therapy using the human multiple drug resistance(MDR) gene in patients with advanced breast, ovarian and braincancers has produced some early promising results. Ironically, theMDR gene is generally regarded as an undesirable gene since it isresponsible for many chemotherapy failures. But Bank hashypothesized that the gene could potentially protect patients from thesevere bone marrow suppression caused by high-dose chemotherapy.

Bank and a team of scientists at Columbia have removed bonemarrow cells from five patients to date and then infected the cellswith a retrovirus carrying the MDR gene. The gene-modified cellswere then returned to the patients' bone marrow. The Phase I trialultimately will enroll 20 patients and will test whether MDR genetransfer can protect hematopoietic progenitor cells (HPC), which areparticularly susceptible to chemotherapeutic agents. HPC in bonemarrow continuously replenish the body's supply of blood cells. Ifsuccessful, MDR gene therapy could be used as an adjunct tochemotherapy, not only to mitigate its most devastating side effectsbut also to allow the use of higher and more effective doses.

BRCA1 Linked To Epidemiology Of Ovarian Cancer

A team of researchers led by Donald Black at the Beatson Institutefor Cancer Research in Glasgow, Scotland, has identified twoparticular mutations of the BRCA1 gene that place women at a higherrisk for ovarian cancer. Tests for the specific mutations couldpotentially lower the death rate from ovarian cancer through earlyidentification and treatment. Ovarian cancer is virtually asymptomaticin its early stages.

First identified in late 1994, the BRCA1 gene is responsible for aninherited susceptibility to both breast and ovarian cancer. Femalecarriers of BRCA1 mutations have an 85 percent lifetime risk ofdeveloping breast cancer and approximately a 50 percent risk ofdeveloping ovarian cancer. BRCA1 germline mutations are believedto account for about 2.5 percent of all ovarian cancer cases and arebelieved to affect about 80 percent of all families with a highincidence of both breast and ovarian cancers.

Tumor Vaccine Enters Phase III Trial

A tumor vaccine targeting advanced metastatic melanoma, the mostserious type of skin cancer, will begin an 842-patient Phase IIIclinical trial conducted by the Eastern Cooperative Oncology Groupby the end of the summer. Researchers are attempting to vaccinatepatients with the ganglioside GM2 to induce a heightened immuneresponse against melanoma cells expressing GM2. Gangliosides aretumor antigens and the GM2 ganglioside abounds in large numberson the surface of melanoma cells but not on normal cells.

The GM2 melanoma vaccine will be evaluated as a second-lineadjuvant therapy for its ability to prevent relapse after standardtherapy. By the year 2000, it's estimated that one in 75 Americanswill be diagnosed with melanoma. n

-- Lisa Piercey Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.