Past Frustrating outcomes Treatment of advanced lung cancer is always frustrating. As early as 2001, the National Institutes of Health (NIH) noted that oncology is the least efficient of the many diseases treated with drugs, with treatment failure rates as high as 70 to 100 percent. In lung cancer, for example, the results of the ECOG 1594 study (1207 cases) published in 2002 showed that the standard three-generation platinum-containing two-drug regimen had a 19% efficiency rate and a 33% 1-year survival rate, and the JMDB study (1725 cases) published in 2008 comparing the efficacy of pemetrexed/cisplatin with gemcitabine/cisplatin showed a 28.2%-30.6% efficiency rate and a 41.6% 1-year survival rate. The 1-year survival rate of patients was 41.9% to 43.5%. Until 2008, lung cancer treatment still seemed to be at the level of “more than 70% of patients with ineffective treatment” given by NIH in 2001. And what about the popular targeted therapies? In the BR.21 study (erlotinib) and the INTEREST study (gefitinib), treatment efficacy was 8.9% and 9.7%, respectively, and it appears that the efficacy of targeted drugs is also very low. Reflecting on where the problem lies, we always prefer one drug to cure all diseases and one regimen to cover the whole world. So, when a new drug is available, we design a study protocol that allows all patients to be enrolled in the study; when a drug is marketed, we like to let all patients try it; we like to say that effective and ineffective, only after trying to know. Of course, the result of this is that we see the so-called bottleneck of efficacy. Breakthrough Constantly segmenting patient groups In the past five years, lung cancer treatment has finally started to try to break through the concept of off-the-charts. On a macro level, it is the continuous segmentation of patient groups; on a micro level, it is the use of biomarkers to guide the selection of treatment for patients. If we must use a new term, it is individualized treatment of lung cancer at different levels. The first factor that comes into our view is behavioral status. Very simply, if a lung cancer patient needs to be bedridden for 50% of the day, that patient is not a good candidate for standard chemotherapy. This is often the case when people say that they are fine without chemotherapy, but they die when they get chemotherapy. Although this is a very important and simple factor, many people, including doctors, still turn a blind eye to it, always thinking that not giving chemotherapy to the patient is equal to waiting for death, and luckily thinking that chemotherapy in this case may be effective and safe, which results in tragedy. The second important factor is the stage of lung cancer. Numerous studies have confirmed that chemotherapy after surgery for stage 1 lung cancer is not only unhelpful but also harmful. Recent studies suggest that chemotherapy given after surgery for stage 1B lung cancer increases the mortality rate by nearly 50% compared to that without chemotherapy, and radiotherapy given after surgery for stage 1-2 lung cancer also increases the mortality rate. With the current clinical data, anyone who recommends adjuvant chemotherapy or adjuvant radiotherapy for stage 1 lung cancer patients is tantamount to a quack. The third important factor is the type of pathology. In the last century, our feeling was that pathological type has an impact on prognosis and may affect the choice of treatment options, but we have been struggling to find evidence, so we simply divided lung cancer into two major types: small cell lung cancer and non-small cell lung cancer and treated them. It was not until 2006 that it was discovered that different pathological types would have different responses and toxic effects to different chemotherapy regimens. As a result, the selection of chemotherapy regimens based on pathological type was written into the clinical guidelines for lung cancer treatment. The selection of patient groups for different treatments based on the clinical factors mentioned above is the germ of individualized medicine. Because of this selection, we have seen some improvement in treatment outcomes: the efficiency rate has increased from 19% in 2002 to 40% currently, and the median survival time has increased from 8 months to 13 months. We should be happy about this, but not too happy: if this is individualized medicine, this individualized treatment may not be a major breakthrough. Turning the corner: A valuable molecular typing was found. This was the year that epidermal growth factor receptor (EGFR) mutations were discovered to be associated with the efficacy of the small molecule-targeted drug gefitinib. A series of clinical trials followed, and by 2010 the dust had finally settled: patients with EGFR mutations, treated first with gefitinib or erlotinib, had a median survival time of more than 23 months. This means that almost half of the patients with advanced lung cancer can survive for 3 years or longer. EGFR mutant lung cancer has become the most significant discovery in lung cancer clinical research in the 21st century. Don’t underestimate the introduction of the concept of EGFR mutant lung cancer, which is actually the first clinically meaningful molecular typing of lung cancer. China has been investing heavily in this work since the end of last century, but unfortunately, there is no original harvest, and the flowers have blossomed abroad. However, there is no doubt that this idea of molecular typing of lung cancer will certainly influence our research and practice for a long time. A good new molecular typing must have a corresponding effective drug or method. This year we have seen another lung cancer molecular typing coming out, which is ALK fusion genotype lung cancer. In the near future, what we may see is cMET amplified lung cancer, KRAS mutant lung cancer, etc. When we can include most lung cancers in molecular typing, individualized treatment of lung cancer can really become a reality. Individualized treatment of lung cancer, reality or dream? According to the current progress, it should be a dream that can possibly come true!