Studying cancer

How goes cancer research? In a nutshell, it’s going well, slowly, but surely.

WHY can’t we cure cancer when we could even land man on the moon back in 1969?

Inevitably, I get asked this question at every cocktail party when I introduce myself as an oncologist. The other common question is “What’s new in cancer treatment?” The somewhat more verbose and erudite will ask “What progress has there been lately in cancer research and treatment?”
Before I answer all these questions, let us get one thing clear. Cancer is not one disease. The word “cancer” encompasses about a hundred different entities.

Basic cancer research – molecular biology, biochemistry, cancer genomics and proteomics – attempts to tease out the similarities and differences amongst all these entities.

Based on this basic research, clinical cancer research is carried out. It usually entails testing out new treatments, eg a new drug, on patients with a certain cancer.

We have new drugs (sunitinib, sorafenib) to prolong the lives of patients with metastatic renal cell carcinoma (kidney cancer that has spread widely in the body).

These drugs are different from the drugs (cisplatinum, vinorelbine) used to improve cure rates in patients who have undergone surgery for early lung cancer.

So, a suitable response to the question “Why can’t we cure cancer” is “Which subset of cancer are you speaking of?”.

For many subsets of cancer, cure is possible. For many others, lives are prolonged with meaning and dignity. For a small subset, we have done less well, but good palliation is always possible.
Sixty years ago, breast cancer was treated with surgery alone. To all intents, women were not given additional treatment (adjuvant treatment in medical parlance) after surgery. At least 80% of patients relapsed and eventually died of advanced metastatic disease.

Forty-five years ago, the first chemotherapy trials were started with CMF, an acronym for the three-drug combination of cyclophosphamide, methotrexate and 5-Fluorouracil.

Tamoxifen, an anti-oestrogenic drug, was introduced for early breast cancer almost 30 years ago. With these early developments in the chemical treatment of early breast cancer, only 50% of patients relapsed.

The 1980s and 1990s saw more chemotherapy agents which were effective in this setting ie early breast cancer. Doxorubicin, paclitaxel and docetaxel produced more cures.

A new class of hormonal therapy with greater efficacy and less side effects, the aromatase inhibitors (anastrozole, letrozole, exemestane), was introduced around the late 1990s.

In the early 2000s, trastuzumab, a highly effective targeted therapy (it targets tumours in 20% of women whose breast cancer expresses the HER2 receptor) was introduced.

Today, the overall relapse rate for early breast cancer is down to 30%!

Of course, each subset of early breast cancer patients will experience a different relapse rate. This only goes to reinforce the fact that cancer is a very heterogeneous disease.

We divide up all cancers into small groups and we divide up these groups again into smaller groups – subsets of subsets if you like. And then we treat each subset differently and achieve different rates of success.

The whole point of taking you through in detail the last 60 years of research and treatment in early breast cancer is to show that it is not an overnight business.

To some, 60 years is a long wait for a 50% gain. The impatient ones would like to see all cancer patients (all subsets, all stages, all scenarios) completely cured today.

In reality, scientific cancer research (a subset of all scientific research) is a slow, laborious, intellectually honest endeavour. It starts with hypothesis generation: based on all we know of this subset of cancer and based on the theoretical actions of the new drug, will it work?

We conduct Phase I trials, then phase II trials and finally the phase III randomised clinical trials. But wait, there is more. Findings of the phase III trials are presented and finally published in a peer-reviewed journal. This new drug will eventually be accepted by the mainstream oncological community and it becomes a new standard of treatment. It takes about 20 years for a drug to get from the “bench to the bed”.

No wonder then that alternative cancer treatment (or under another guise, traditional and complementary medicine) is so attractive to so many. It meets many unmet needs with so little hassle. There is no need to trawl through all the available data and scientific methodologies.

Nothing is obvious in science. Nothing is taken for granted. No leaps of faith and no extrapolations here.

Trastuzumab was initially shown to work very well in advanced breast cancer. A 50% response rate was obtained and lives were prolonged.

By simple deduction, trastuzumab should work even better in early breast cancer where the tumour load is much smaller. Yet four randomised clinical trials were conducted at the cost of US1.2bil (RM4.08bil) to see if this drug will also work in early breast cancer. The findings of these trials have now conclusively proven that trastuzumab works very well in early breast cancer.

What of the next 60 years of scientific research in cancer?

Expect more and watch this space carefully. But don’t look for that quick unproven fix offered at every dark street corner.

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