Episode 4. Bleomycin: It’s personal

In the lab, I deposited a drop of bleomycin solution on the epiglottis of a rat. I twirled the animal a little, and it aspired the bleomycin into its lungs. Over a few weeks, the bleomycin will accumulate, break the DNA strands and kill the epithelial cells in the animal’s alveoli. Reactive oxygen species will be generated, activate macrophages, and inflammation will result, leading to pulmonary fibrosis.

Mechanism of disease induction: apoptosis leading to inflammation and collagen deposition.

With the animal thus induced, I returned my lab coat to its hook, grabbed my hat, and drove 6 km to the local hospital: time for my chemotherapy treatment. Seated in an infusion chair, I’m efficiently connected to an i.v. pump via my “Peripherally Inserted Central Catheter (PICC line)”. The 43 cm-long PICC line starts in the vena cava short of my right atrium, and exits under the bicep of my left arm. My heart will pump through my body the perfusate delivered via the PICC line.

Dosing today against testicular cancer: Bleomycin.

In my bloodstream, bleomycin will accumulate, break the DNA strands and kill the rapidly-dividing cells in the tumors I’m trying to eliminate. Reactive oxygen species will be generated, activating the macrophages who will chew up the mass of cells called “cancer”. And a bunch of other cells I’d have left untouched, personally.

Mechanism of efficacy: apoptosis leading to inflammation and macrophage assault on the tumoral cells.

Fifty-two years ago, the association between bleomycin’s efficacy against the DNA polymerase and its anti-cancer potential was evident enough to warrant publication by T. Kobayashi (1). Thankfully, his typewritten data tables successfully argued in favor of using bleomycin against cancer cells: millions of patients have been treated with it, alone or in combination.

A year later, Flandres (2) reported on the creation of lung disease by bleomycin, thus setting the table for its use to induce pulmonary fibrosis in preclinical models. In 2023, the rodent bleomycin model remains the gold standard for testing the efficacy of new drugs aimed against human idiopathic pulmonary fibrosis, including the two standards of care (Pirfenidone and Nintedanib).

The translatability of bleomycin’s cell toxicity from rodents to humans created the oncology drug, and the pneumology preclinical tool to develop countless other drugs against IPF. Perhaps bleomycin is a poster child for the old adage saying that “all drugs are toxins”.

1.       Kobayashi T. Reduced activity of DNA polymerase prepared from bleomycin-treated cancer cells. J Antibiot (Tokyo). 1971; 24(8):519-25.

2.       Flandre O, Beaulaton IS, Damon M, Allieu M. Etude expérimentale de la production et de la prévention des pneumopathies observées au cours des traitements par la bléomycine Therapie. 1972; 27(1): 67-76.