New treatments for rare cancers
There is a deep need for new therapeutic options for rare cancers like sarcoma. In Jørgen Wesche`s group in CanCell we evaluate whether new drugs developed for other cancer types can improve sarcoma treatment.
Recently, I attended a meeting where cancer survivors told their stories. They spoke about how they experienced their diagnosis, the treatment period and how they managed life after surviving cancer. One young girl made a strong impression on me and the others in the audience.
As a teenager, the young girl got an aggressive form of sarcoma. This is a rare type of cancer that arises in fat, bone, connective tissue, or muscles. Her treatment included a combination of surgery, chemotherapy, and irradiation, and later bone marrow transplantation. Luckily, this treatment eradicated the tumor, and five years later there were no signs of relapse. She was cancer free, a survivor! However, the treatment was not without a cost.
New cancer treatments improve many patients’ prognosis, and many more patients survive their disease today than before. Historically, cancer treatment has involved drugs that kill dividing cells. Unfortunately, healthy cells in the body will also be affected by this treatment. A challenge with cancer treatment is that many patients experience severe side effects, both during treatment and when returning to their daily lives. The young girl at the conference explained how the cancer treatment had removed her chances to become pregnant. The treatments also reduced her ability to work full time due to fatigue, and she had become more vulnerable for infections, and this affected her social life.
Doctors group cancer patients according to the place of the tumors in the body, and cancer treatment is traditionally given based on the type of tumor the patient has. Some cancer types are frequent, like breast, lung, and colon cancer, and large groups of patients are a priority for pharmaceutical companies that develop new drugs. However, there is less economical interest in developing therapeutics for more seldom tumor types, like sarcomas.
Instead of targeting rapidly dividing cells, newer cancer drugs target the underlying molecular mechanisms that drive tumor growth. In many cases, these are changes (mutations) in specific genes that allow the cancer cells to grow uncontrolled. Drugs that specifically target cells with mutations should ideally be tumor specific, leave healthy cells alone, and give fewer side effects to the patient. However, drugs never have absolute specificity, and some side effects may remain.
The cancer specific mutations occur in a subset of patients within a tumor type, and identification of these patients allows personalized treatment. Interestingly, the same mutation can also be found in patients with unrelated tumor types. Both patients could benefit from the same drug. The new strategy for cancer treatment is to select drugs based on the mutation(s) found in the tumor, and not just where the tumor was localized.
I work with cancer research at Oslo University Hospital in the “Molecular Biology of Sarcoma”- group headed by Jørgen Wesche, one of six leaders in CanCell. I evaluate the effect of new cancer drugs for sarcomas, as part of a large multidisciplinary project led by Ola Myklebost. In particular, we investigate if drugs that target cancer cells with specific mutations can be used in treatment of selected sarcoma patients (https://nosarc.no).
To do this, we have sequenced and evaluated all cancer relevant genes in sarcoma cells in the laboratory. When we identify a potentially targetable mutation, we evaluate if the sarcoma cells in the laboratory respond to the drug in a manner similar to tumor cells from the tumor type the treatment was originally derived for. Especially, we evaluate the drug’s abilities to reduce cell growth and to kill cells. If the response is promising, the drug should be further investigated in in vivo models generated from sarcomas and in the end also in clinical trials. In this way, we hope to identify new potential treatments for patients with very limited treatment options, without the high economical cost related to drug development.
For future patients with a rare cancer type, such as sarcoma, this could mean to survive like the young girl in the conference, but without life long side effects of the treatment.
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