Emerging targets for the treatment of lung cancer

Share :
Published: 26 Jul 2017
Views: 4745
Prof Tarek Mekhail - Florida Hospital Cancer Institute, Orlando, USA

Prof Mekhail speaks with ecancer at NOSCM 2017 targeted therapies for lung cancer.

He looks beyond EGFR and ALK mutations to emerging targets in lung cancer including BRAF and HER2, which have significant histories in other disease but are now becoming apparent as lung cancer drivers, and rearrangements in MET and RET genes.

Prof Mekhail also discusses immune evasion of tumours, and how immunotherapies can reawaken immune cells to clear cancer cells.

Targeted therapy for lung cancer was also discussed at NOSCM 2017 by Dr Luis Raez, here, and at the 2017 WIN symposium by Dr Reinhard Büttner, here.

My talk is about targeted therapy in lung cancer. Over the last few years we realised that not all lung cancers are the same. In the past we treated all non-small cell lung cancer in a similar fashion and then we evolved to differentiate based on the histology. Right now we’ve evolved in completely new ground where we differentiate the treatment of lung cancer based on oncological markers. The most famous of these oncological markers is EGFR mutation and the ALK translocation where targeted therapy to this particular molecular aberrance has significant impact on the outcome of lung cancer. That’s not actually my talk today, that’s the talk prior to my talk; my talk was the other newer oncogenic targets that have been discovered in lung cancer since then.

So I’m going to cover three or four of these new oncogenic targets: the BRAF, which is a well-known mutation that happens in melanoma and lung cancer and perhaps in some other rare malignancies like thyroid cancer. It turns out that targeting this oncogenic driver in melanoma is very useful for the melanoma patient. We have data now in lung cancer that it’s also useful in lung cancer.

I’m going to also cover the HER2 amplification which is very famous in breast cancer and very unfamous in lung cancer but it turns out that in lung cancer there is utility for targeting that gene as well. We’ll cover two other areas which is MET exon 14 skipping as well as the RET oncogene.

It highlights the significant change in our mind-set on how to treat lung cancer. Instead of treating all lung cancer patients the same we are identifying small subsets of people. So instead of saying all lung cancers or adenocarcinoma, which is 100,000 patients a year in the United States for adenocarcinoma, 120,000, perhaps another 60,000 or 80,000 for squamous cell carcinoma. We used to treat these 120,000 or 130,000 in a very similar fashion, now we are identifying subsets of patients. This couple of thousand patients have that oncogenic driver and there is a new drug for this. So all these new drugs are targeted drugs in general that benefit a subset of patients and that is the era of personalised medicine.

There is also a new class of drugs that might not be as specific as this targeted therapy which is immune therapy. When we talk about immune therapy we are really targeting the immune system of the body, awakening the immune system to the presence of the cancer. Cancer exists in our body because the body is not fighting it and the reason it’s not fighting it is cancer evades the immune system. We have understood the mechanisms by which cancer evades the immune system: it could be by secretion of an enzyme and the abbreviation for that enzyme is IDO, without going into the full name; by expression of a factor like PD-L1 on the surface of the cancer cells and this interacts with the immune system of the body and basically puts the immune system to sleep. A new class of drugs that awakens the immune system by making the immune system see the cancer as a fault and starting to attack. These treatments are not necessarily as specific as targeted therapy but that’s a good thing as well because it might benefit a larger proportion of patients.

Are there complications from these treatments?

It’s a new spectrum of side effects. I must, however, say that it’s a completely different bar, that we’ve now raised the bar. If I present the types of drugs we used to treat cancer with twenty years ago and presented to ourselves or our patients now we would be laughing at ourselves. We treated cancer in the past with drugs that can cause significant nausea, can cause significant peripheral neuropathy in a large proportion of patients. Now we are dealing with drugs that still have side effects but the side effects, maybe it’s new types of side effects, but affect a handful of the patients. By no means I want to underestimate the importance of a 5% incidence of side effects but it is not 20% or not 30%. We need to educate ourselves how to avoid these particular side effects. We need to be aware that they can happen and can be life-threatening.

But the idea of treating cancer patients now is not to have the patient have the stigma of a cancer patient getting treatment. You would be able to identify cancer patients from a distance – this is a cancer patient getting treatment. With the treatment nowadays we are giving patients are living a near normal life. I can say that many of my patients are having a completely normal life with very manageable, very little side effects and life completely normal activity, perhaps go back to work. That’s the idea of making cancer a chronic disease in which patients can tolerate that cancer as well as be functional and enjoy quality of life.