Razor sharp precision, with a personalised touch

 

When you go to the shops, the fitting guide does not necessarily give you the best ‘fit.’  When a cancer patient begins treatment, the generic prescribed course of action may not give them the best ‘fit’ either.

Following on from my cold-stress tumor model post, one post got me thinking about far more precise, accurate treatments- ones that move away from quite harsh, generic chemo and radiotherapy regimes

In 2010, Elaine Mardis and her colleagues came across a patient suffering from leukemia, after a series of confusing diagnoses. The patient suffered from acute promyelotic leukemia (APL)- one of the most treatable forms, in which parts of chromosome 15 and 17 switch places, triggering an excess level of blood forming cells. However, other features of her chromosomes suggested that she might have a much more dangerous version of APL, which would require a blood marrow transplant.

Mardis is a firm believer of whole genome sequencing and other analyses, to launch precision attacks against difficult cancers.  Her colleagues sequenced the patient’s genome, to discover that she indeed only had a piece of chromosome 15 attached to 17, therefore she would respond to traditional APL treatments. The patient avoided a risky bone marrow transplant, while having the confidence that her current treatment would keep her cancer at bay.

 

One size does NOT fit all

While medical treatments in the past, including those for cancer, where generally a case of ‘one size fits all,’ now we face the advent of precision cancer treatments. Consider it this way: rather than going to a suit store, and buying a generic sized coat, hoping that we adequately fit the range, we can now go to the tailor, and get a suit made to order, ensuring a perfect fit. This is the situation that is now beginning to come to fore in cancer treatment. However, while personalized cancer treatment shows great promise, the field is still limited by many complexities and constraints.

Generic treatment regimes are NOT specific enough  Credit Chris Goldberg [ CC BY-NC 2.0]
Not the perfect fit: Generic treatment regimes are NOT specific enough
Credit Chris Goldberg [ CC BY-NC 2.0]

Researchers believe that if they can find the key genetic mutations that drive a particular cancer’s growth, they will be able to target the tumor more selectively, with fewer toxic side effects.

Each type of cancer is a formidable opponent, however like each opponent, they have an inherent weak spot- a genetic vulnerability that can be exploited to our advantage.  This weak spot can be the target of the right drug, in a future in which the genome of each cancer will be sequenced, and then paired with an appropriate, target specific treatment.

 

 A specific sucker punch

Consider Imatinib’s success: a target specific drug fighting against chronic myelogenous leukaemia (CML)- a rare blood cancer. A patient’s genome is compared to a target panel of genes, allowing doctors to determine if the patient is suitable for the drug. In the past, unless these patients received a bone marrow transplant, they would die in approximately 5 years. Now their life span is at least 20 years, post diagnosis.

However- imatinib’s success is not easy to replicate- each tumor has a distinct set of genetic mutations- no two tumors are genetically the same. This heterogeneity extends to a cellular level within a single tumor- meaning that matching a patient with a particular treatment can be a very difficult process.

However, what drugs such as Imatinib capitalize on are the driver oncogenes of a cancer- the ones that drives cancer’s growth. There are a tiny amount of oncogenes, roughly 200-300 common ones. Understanding how to disable common driver oncogenes should therefore allow the treatment of a large amount of cancers.

Currently, oncologists classify cancer by which organ it first appeared in. However, by using genetic profiling of tumors, a shift in thought is required, meaning we must classify cancer based on its genetic code, not how it looks under the microscope.

Change in approach: classification of cancer needs revision Credit Gerry Lauzon [ CC BY 2.0]
Change in approach: classification of cancer needs revision
Credit Gerry Lauzon [ CC BY 2.0]
 Interestingly, there are commonalities between frequent mutations observed in breast cancer, and those seen in all forms of thyroid cancer, leukaemia and lymphoma, further proving the above point. Cancer biologist Jose Baselga and his colleagues are pushing this change in thought, developing clinical trials that group patients by genotype, rather than cancer’s organ of origin.

 

Time management

Precision medicine will also depend on timely delivery of medication- this requires not only knowing which mutations get a tumour started, but also how the tumour is likely to change.

This can be monitored via scraps of DNA from blood samples, making it possible to determine accurate biomarkers for the disease over time.

Sarah Jane Dawson, a molecular biologist and oncologist at Peter Mac, studies cell-free DNA: genetic material that has escaped into circulation from dying cells. She has found that changes in cell-free tumour are detectable, on average 5 months before any changes to a patient’s cancer are seen in any scans.

This is the future- viewing cancer as a set of genetic mutations, identifying their weak spots, and exploiting them with just the right drug, at just the right time.

While great promise lies in complementing current cancer treatments, such a radio and chemotherapy, perhaps we stand to reap the greatest rewards by going one step further, and redefining how we fight cancer. Rather than throwing a cocktail of stock standard treatments at our patients, perhaps a more personalised touch will do much more good.

Link to article

http://www.scientificamerican.com/article/therapy-this-time-it-s-personal/