Systemic toxicity, severe side effects, and resistance that leads to recurrence and metastasis.
Drugs should heal, not kill.
Whether the negative effects are imminent or slowly manifesting, they matter.
The first generation of cancer drugs was cytotoxic chemotherapy, developed by modeling mustard gas used in World War I. Given this history, it is not surprising how toxic it is; what is surprising is that it remains the standard of care for many neoplasia even today.
The second generation of cancer drugs is targeted therapy that aims to specifically target molecular pathways. Although termed “targeted,” often it targets pathways that are highly active not only in cancer cells, but also in healthy stem cells, leading to long-lasting side effects. More importantly, it is always very vulnerable to resistance, which easily leads to cancer recurrence. Cancer consists of highly adaptive, mutating cells. The more “targeted” it is, the easier it is for cancer cells to mutate what is being targeted and become resistant to the drug being used.
The third generation of cancer drugs is immunotherapy. Most immunotherapy drugs still target single receptors or molecules on immune cells or cancer cells and have the problem of low efficacy, some off-target toxicity to stem cells, and a high risk of recurrence.
Till when will we be okay with cancer drugs that, at most, elongate survival for a few years at the cost of severe side effects and the ever-present fear of recurrence and metastasis?
Lasting higher efficacy and safety can be achieved only by using a fundamentally different approach that considers both from the very beginning.