What Factors Contribute to Trastuzumab Resistance?

Resistance to trastuzumab, a cancer medication, can occur for a variety of genetic and environmental reasons. This drug targets a specific receptor known as HER2 found in some breast cancer cases. It inhibits cell growth, halting further development of the cancer, and can be used in combination with surgery, radiation, and other chemotherapy drugs. Treatment with trastuzumab can improve outcomes for breast cancer patients, especially when it is used in combination therapy, but some tend to develop resistance to the drug when used over a period of time.

In some cases, a patient successfully treated with trastuzumab initially develops a recurrence, in which case the new tumor is likely resistant to the drug. Other patients may experience initial success on trastuzumab, only to find that the tumor starts growing again and shows signs of resistance. Some may experience poor outcomes on trastuzumab therapy from the start. The reasons for this are complex, and involve changes to molecular signaling pathways involved in cancer growth.

Like other cells in the body, cancer cells adapt to their circumstances. In treatment with trastuzumab, the tumor learns that it cannot keep growing, and it develops workarounds. It can send signals to increase the expression of some molecular compounds, or to suppress others. If it can successfully change the patient's signaling pathways, it can start growing again. Some of the compounds involved in trastuzumab resistance include glycoproteins, tyrosine kinases, and microRNA.

The genetics of each patient are slightly different and can contribute to trastuzumab resistance in various ways. In patients with HER2 sensitive breast cancers, some may have a genetic predisposition for trastuzumab resistance. These patients will develop signs of resistance earlier than others, and may not experience positive outcomes with their cancer therapy. Others may have more forgiving genetics, and their cancers take longer to figure out how to short-circuit the medication and keep growing. It can be hard to predict which patients will respond best.

Management of trastuzumab resistance can take a number of approaches. One option is combination therapy to keep the tumor under attack so it cannot develop resistance as quickly. It is also possible to administer medications to block some of the signaling pathway changes. For example, if the tumor directs the body to produce more of a given compound, a drug can block production, thwarting the tumor's attempt to develop trastuzumab resistance. Research on cancer therapy includes exploration of a number of options for treating medication-resistant cancers and improving patient outcomes.