Scitech | Progress in cancer research

A perspective from the case of medulloblastoma

Cells in our body usually operate in an orderly fashion: they divide and undergo apoptosis as the body needs them. However, cancerous cells grow and divide uncontrollably; they don’t undergo their programmed deaths when they are damaged. Cancer often appears in the form of a mass of cancerous cells, known as a tumor. Some cancers are malignant, meaning they can break off from their source of origin and invade other healthy tissues, creating havoc and breaking things one by one. One month a patient might see a mass on their chest, the next the patient might have a hard time breathing. The cancer has spread from one place to another, and this is called metastasis. Cancers can start anywhere in the body: blood, bones, or internal organs.

The primary cancer treatments are chemotherapy, radiotherapy and surgery. However, depending on the type of cancer, one treatment may work and another may not. Through chemotherapy, an oncologist applies several drugs to reduce and remove a tumor. During radiotherapy a doctor beams radiation to trim down the tumor size. Chemotherapy and radiotherapy are employed first, followed by surgery. In surgery, a surgeon cuts a chunk of the targeted organ where the tumour lies.

One month a patient might see a mass on their chest, the next the patient might have a hard time breathing.

Medulloblastoma is a cancer that originates in the cerebellum, a part of the brain that coordinates movement and balance. 75% of the affected patients are under ten years old. Following primary cancer treatments, severe side-effects occur including neurocognitive deficits, endocrine problems, meningioma and sterility. Many healthy organs are subject to toxic damage from sessions of chemotherapy. This damage is even more severe in children because their cells divide more quickly, meaning the spread of toxins is faster. Surgery also carries high risks as the cerebellum is located just above the spinal cord.

To look for alternative treatments, a research group in Tennessee suggested a new strategy to treat medulloblastoma. The Tennessee group used a novel molecule named HHAntag691 that blocks a pathway named Sonic Hedgehog (SHH). When the SHH pathway is active, the cells in the cerebellum called granule cell precursors multiply uncontrollably, and medulloblastoma appears. Through the action of HHAntag691, the rampant proliferation stops.

Many healthy organs are subject to toxic damage from sessions of chemotherapy.

This method was later tested in clinical trials. In 2008, a patient was treated with a similar but not identical molecule to HHAntag691 during clinical trial phase I – this is the phase when scientists apply drugs of interest that they had used on animals to humans. Before the treatment, the cancer had already spread. After the treatment, the cancer disappeared completely in 2 months. Sadly, the patient died 3 months after the treatment when the tumor relapsed. This was because a mutation had occurred, altering the SHH pathway and rendering the drug ineffective. Although unfortunately the patient did not survive, this was the first successful case of targeted-therapy, where only one type of cancer is tackled.

Passing the four phases of a clinical trial is required to get a drug approved. Vismodegib, the commercial name of the drug that has completed the first case of targeted therapy, is at phase II. In 2015, the drug worked better in Medulloblastoma patients who had a mutated SHH pathway than the ones with no mutation in the SHH pathway.

Medulloblastoma shows how powerful a cancer can be. Scientists have painstakingly developed new strategies to provide target-specific treatments against cancer, but it only takes one mutation from a cancer cell for a patient to become drug-resistant. Perhaps one obvious reason that cancer is like a death sentence to us is that it morphs our fundamental biological processes to favor itself. So despite advancements, it seems cancer research still has a long way to go.

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