Global cancer rates are set to
jump 50% by 2020, putting cancer on course to overtake
heart disease as the number one killer. But things are
also moving quickly in the search for new drugs to fight
it.
This year's meeting of the American
Society of Clinical Oncology (ASCO) saw presentations
on more new cancer drugs, with more new mechanisms of
action, than ever before. In fact, nearly half of all
the drugs currently under development " about 400 "
target some form of the disease. And for the first time,
many of them come in much sought-after pill form.
Among the new stars unveiled at
the ASCO meeting in Atlanta this month are lapatinib
(Tykerb), which takes aim at breast cancer; sunitinib
malate (Sutent), already on the market for kidney cancer
but showing promising new data; and the experimental
Apo2L/TRAIL, which animal studies suggest could trigger
cell death in colon, lung, breast, prostate and melanoma.
ONE,
TWO PUNCH
Although lapitinib (Tykerb) has only finished a phase
I trial, the data show that 46% of breast cancer patients
had stable disease or tumour shrinkage after taking
the pill for eight weeks. Duke Comprehensive Cancer
Center oncologist Dr Kimberly Blackwell, who presented
the findings, noted that lapinitib targets two growth
factors: the Her-2 estrogen receptor and the so-called
epidermal growth factor receptor.
"Blocking the action of two growth
factors has a more profound effect on inhibiting cell
growth than blocking a single growth factor, and we
think this dual action on breast cancer cells is responsible
for the positive effects we're seeing," she said. Nearly
a third of patients with Her-2 overexpressing cancer
don't respond to trastuzumab — the gold standard
treatment for this invasive form of breast cancer —
and most of the subjects in this trial had already tried
several traditional cancer drugs. What's more, there's
some evidence that unlike trastuzumab, lapitinib can
cross the blood-brain barrier, thus gaining access to
tumours that have spread from the breast to the brain.
ONE
BETTER
Sunitinib malate (Sutent), an anti-angiogenic agent,
is already on the market for kidney cancer, but data
indicate the drug is in fact more effective than the
current standard treatment — immunotherapy with
interferon-alpha (IFN-a) for patients with the advanced,
metastatic form of the disease. The study, presented
by oncologist Dr Robert J Motzer of Memorial Sloan-Kettering
Cancer Center in New York City, included 750 patients
over 60 treated with a six-week cycle of sunitinib.
Median progression-free survival was 11 months in those
receiving sunitinib, compared with five months for those
receiving IFN-a. "This drug has shown more activity
as a single agent against advanced kidney cancer than
any other drug I've studied in the past 15 years," Dr
Motzer said.
But it gets even better. Sunitinib
may have a role to play in non-small cell lung cancer
as well, according to a presentation by Dr Mark Socinski
of the University of North Carolina at Chapel Hill.
"As a single agent, this drug worked in a difficult
group of patients whose advanced disease had been previously
treated with other chemotherapies and whose options
were limited," he said.
During a six-week treatment cycle
in 63 patients, researchers observed six "partial responses"
and saw disease stabilized in a further 27 patients.
No actual survival data is yet available, but a subgroup
of 47 patients is continuing to take the drug. Like
lapitinib, sunitinib comes in pill form — which
is much more agreeable to patients than intravenous
delivery.
SUICIDE
KING
The much-anticipated results of the first phase I trial
of a drug designed to target the "death receptors" on
cancer cells were also promising. Fifty-eight patients
with a variety of advanced cancers are participating.
The drug, Apo2L/TRAIL, shrunk tumours in one patient
with sarcoma and stabilized disease in 56% of participants,
said Dr Roy Herbst, chief of thoracic medical oncology
at the MD Anderson Cancer Center in Houston.
It's too early to pronounce on
efficacy, he said, especially as the maximum tolerable
dosage has yet to be found. But "this is an interesting
new class of targeted agents," he said. "Normally, the
p53 gene regulates cell suicide in the presence of cell
damage, such as that induced by chemotherapy and radiotherapy."
But p53 inactivated in more than half of all cancers.
"We expect this agent to work even in those patients
with mutated p53," Dr Herbst said.
CANCER-KILLING
COCKTAIL
One weakness of targeted drugs is that they're likely
to work only in a subset of patients, and there are
few reliable methods of determining who is likely to
benefit from what. Even when the patient responds, resistance
is likely to develop as the few cancer cells that can
stand the treatment preferentially reproduce.
Dr Jose Baselga of Vall d'Hebron
University Barcelona told the ASCO conference that the
proliferation of new, targeted drugs could offer a way
around this problem. Just as various less-than-perfect
HIV drugs were combined to form a highly effective triple
therapy, so the various targets of the new cancer drugs
should be hit simultaneously to nip any potential resistance
in the bud. "We now have increasing evidence in the
lab that if you hit cancer cells on two different steps,
you can induce very severe damage and cell death," he
said.
These targeted therapies, said
Dr Baselga, are the practical application of the theory
of "oncogene addiction". This concept, which is rapidly
gaining ground among specialists, holds that the very
abnormality of the oncogene, which drives the cell toward
malignancy, also alters cell-signalling pathways in
a way that makes the cell absolutely dependent on that
oncogene to survive.
Oncogene addiction has been described
as the Achilles heel of cancer cells. "It gives them
tremendous growth capacity, but at the same time they
are extremely fragile," said Dr Baselga.
"We have new therapies that are
very active in cancer and yet they have minimal side
effects in patients. The only explanation for that is
that they have differential sensitivity " cancer cells
can't tolerate [them], while normal tissues can live
with it. So we may be closer than we think to having
profound effects on cancer."
Cancer cells, he added, are "not
as resourceful as we sometimes tend to think."
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