How a customized solution can improve lung cancer outcomes
Author: Hirva Mamdani, M.D.
Originally posted on KevinMD.com
Why does one person respond favorably to lung cancer treatment while another does not?
The answer lies in the DNA of cancer cells.
Just 20 years ago, lung cancer was broadly categorized into two groups based on the microscopic appearance of the tumor cells: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Relatively recently, the treatment of NSCLC shifted from dependence on chemotherapy as a single treatment option to treatment with precision medicine -- a more individualized treatment based on the genetic profile of a patient’s cancer. This significant advancement is positively impacting survival rates.
In the 2010s, researchers and clinicians started to understand the fundamental biological differences between the two most common subtypes of NSCLC (adenocarcinoma and squamous cell carcinoma), which provided insight into why certain patients had greater success with treatment. While these biological differences explained some of the discrepancies in the survival pattern, much remained unknown.
A breakthrough occurred when we discovered specific gene mutations within the tumor called ‘driver’ mutations. The development of medications specifically targeting these driver gene mutations ushered in the era of precision medicine in lung cancer and allowed us to uncover foundational differences in the DNA of lung cancer tumors.
This discovery and many more that followed established that each lung cancer tumor is unique and has its own genomic structure. It allowed us to transition from a ‘one size fits all’ to a ‘custom made’ approach. And our bespoke treatments are working. Treatment with targeted therapies has led to improvement in overall survival and quality of life of patients with advanced non-small cell lung cancer.
Precision medicine or personalized medicine has many benefits, but the greatest is that it allows patients to get the treatment that is most likely to work for them while reducing drug toxicity. Essentially, we can pull the most effective tools from our toolbox, rather than pulling them all out at once or following a more generic protocol.
That’s the good news, so what’s the bad news?
Many cancer patients do not undergo comprehensive genomic testing. Testing for common targetable gene mutations/alterations is becoming common practice in oncology. Unfortunately, this process does not typically include testing for less common genomic alterations. As a result, targetable mutated genes can go unnoticed.
Another downside is that even if a patient has access to comprehensive treatment, some genomic alterations are not currently treatable with targeted therapies. However, identifying these alterations may provide clinicians with vital insight so they can rule out which therapies will not work or may potentially negatively impact the efficacy of other treatments. Additionally, while some alterations may not be targetable with an FDA-approved therapy at this time, clinical trials may provide additional future options. Overall, access to more comprehensive testing is ideal because if a rare gene mutation is identified that cannot be treated with targeted therapies, clinicians obtain valuable knowledge so they can provide better, more precise treatment options.
It is exciting and encouraging to see new treatment options being developed from life-saving clinical trials. For example, in May, a new drug was approved to target a specific subset of KRAS gene mutations. This abnormality is present in about 13% of lung cancers. While the KRAS mutation was identified in 1983, it was 2021 before we had a breakthrough in targeting it. This new option provided a fresh path for patients who may have otherwise run out of options. We know even more progress will be made through research and clinical trials.
We are making breakthroughs in cancer treatment every day, and our ability to treat patients more effectively will continue improving as genomic profiling advances. I encourage all patients who are diagnosed with cancer to talk with their doctor about individualized treatments. I also encourage patients to discuss clinical trials, which truly are the medicine of tomorrow.
We now have capabilities that allow us to better understand why every person responds to cancer differently. More importantly, we are creating the tools that can provide unique treatments for every cancer journey. With targeted therapies, we are moving toward a world free of cancer.