This document provides an overview of recent advances in lung cancer research. It discusses the types of lung cancer and treatments such as chemotherapy, immunotherapy, and targeted therapies. New discoveries include approval of the first KRAS inhibitor drug and combinations of chemotherapy with drugs that inhibit DNA repair. Ongoing areas of research focus on biomarkers, immunotherapy, liquid biopsies, robotics for surgery, and stereotactic radiation. The future for lung cancer treatment is promising with decreasing mortality rates resulting from new targeted therapies and increased use of screening.

1. Prepared by - Rohan Jagdale, YTIP MUMBAI
Advances in
Lung Cancer Research

2. Serial No. Topics Slide No.
1. Introduction 3
2. What is lung cancer and Types 4
3. Lung cancer treatments 7
4. New Discoveries in lung cancer research 11
5. Latest articles on lung cancer research 13
6. 5 Important Areas of Lung Cancer research 28
7. Future of lung cancer treatment 39

3. Introduction
● Lung cancer is the deadliest cancer and makes up
approximately 25% of all cancer deaths. Every year, there are
more lung cancer deaths than breast, colon and prostate
cancers combined.
● However, thanks to ongoing research efforts, new lung
cancer cases are declining, and the number of deaths has
decreased thanks to early detection and advanced treatment
options.
● Discoveries in lung cancer research are leading scientists
closer to a cure, and every step forward also aids efforts
towards treatments for other lung diseases.

4. What is lung cancer?
● Lung cancer occurs when cells divide in the lungs
uncontrollably. This causes tumors to grow. These
can reduce a person’s ability to breathe and spread to
other parts of the body.
● Lung cancer can be fatal, but effective diagnoses and
treatments are improving the outlook.
● Anyone can develop lung cancer, but cigarette
smoking and having exposure to smoke, inhaled
chemicals, or other toxins can increase the risk.

5. The two main types of lung cancer are small cell
lung cancer and non-small cell lung cancer,
depending on how they appear under a
microscope. Non-small cell lung cancer is more
common than small cell lung cancer.

7. Lung cancer treatments
The type of treatment a patient receives for lung cancer
may depend on the type of lung cancer and whether the
disease has metastasized (spread) to distant to distant
organs. The types of lung cancer and their treatments
include:

8. Small cell lung cancer:
This type of lung cancer may be aggressive and may require
immediate treatment. Treatments for small cell lung cancer
include:
● Chemotherapy
● Immunotherapy
● Laser therapy
● Radiation therapy
● Surgery

9. Non-small cell lung cancer:
This is the most common form of lung cancer. Treatments for
non-small cell lung cancer include:
● Chemotherapy
● Cryotherapy
● Immunotherapy
● Laser therapy
● Photodynamic therapy
● Radiation therapy
● Surgery
● Targeted therapy

10. Metastatic lung cancer:
In general, metastatic cancers are treated based on which part of the body
the cancer first formed, so metastatic lung cancer is often treated as an
advanced form of the disease, even if it spread to distant parts of the body.
Immunotherapy and targeted therapy may be recommended to treat
metastatic lung cancer. Other treatment options may depend on where the
cancer has spread. For instance:
● Options for brain metastases include radiation therapy, chemotherapy
and/or steroids.
● If the cancer has spread to the bone, radiation therapy or targeted
therapy may be recommended.

11. New Discoveries in Lung Cancer Research
The overriding message in lung cancer treatment today is that
every patient needs a customized treatment plan. One
designed for the exact molecular features of their tumor.
Matching the right treatment to the right patient is improving
outcomes for this disease.

12. Over the past few years, there have been revolutionary
advances in techniques such as:
● detection
● surgery
● radiation
● treatment protocols

13. Latest articles on lung cancer research
➢ FDA Approval of KRAS Inhibitor Sotorasib for Lung Cancer
Hailed as Milestone
➢ Topotecan–Berzosertib Combination Shows Promise against
Small Cell Lung Cancer
➢ Osimertinib Improves Survival in Advanced Lung Cancer with
EGFR Mutations

14. FDA Approval of KRAS Inhibitor Sotorasib for Lung
Cancer Hailed as Milestone
Doctors and scientists have known for decades that harmful
mutations in a gene called KRAS are the root cause of cancer
for hundreds of thousands of people. But there have been no
effective treatments that counteract the cancer-fueling
actions of mutant KRAS proteins—until now. On May 28, the
Food and Drug Administration (FDA) granted accelerated
approval to the first KRAS-blocking drug, called sotorasib
(Lumakras).

15. Sotorasib
KRAS drug sotorasib

16. Under the new approval, sotorasib can be used to treat
people with non-small cell lung cancer (NSCLC) that
has spread nearby (locally advanced) or to distant
locations (metastatic) in the body. Patients must have
previously received at least one other systemic cancer
treatment, such as chemotherapy, and have a
particular KRAS mutation, known as G12C, in their
tumors.

17. Mutated KRAS-driven lung cancer cells (purple) in a
genetically engineered mouse model of lung cancer.

18. Topotecan–Berzosertib Combination Shows
Promise against Small Cell Lung Cancer
Researchers have identified a combination of two drugs that
can shrink the tumors of some patients with small cell lung
cancer (SCLC), the most aggressive form of lung cancer.
Many patients with SCLC respond to an initial treatment with
chemotherapy and/or immunotherapy. But the cancer usually
comes back and does not respond to additional chemotherapy.
At this point, the disease is typically fatal within a matter of
weeks.

19. The new combination therapy includes the
chemotherapy drug topotecan (Hycamtin),
which is FDA approved for some patients with
SCLC, and the investigational drug berzosertib,
which inhibits a protein that helps repair
damaged DNA.

20. A small clinical trial tested the combination of topotecan with the drug
berzosertib, which inhibits a protein that helps repair damaged DNA in cancer
cells.

21. chemotherapy drug topotecan (Hycamtin)
topotecan

22. Berzosertib
Berzosertib (formerly M6620, VX-970) is an intravenous (i.v.),
highly potent (IC50 = 19 nM), and selective, first-in-class ATR
inhibitor. Preclinical studies of berzosertib have shown synergy in
combination with cisplatin, which led to anti-tumour responses in
patient-derived lung cancer xenografts that were otherwise
insensitive to cisplatin monotherapy.

23. ● Both drugs are given intravenously. “The sequence of
administration of the two drugs is important,”
● “In the laboratory researchers found that the most
effective strategy was to give both drugs together,
and the same dosing strategy was used in the clinical
trial.”
● The results need to be confirmed in a larger clinical
trial, which is underway, the research team wrote.

24. Osimertinib Improves Survival in Advanced Lung
Cancer with EGFR Mutations
The first therapies that target mutated forms of the EGFR protein
were approved for use in people with non-small cell lung cancer
(NSCLC) more than 15 years ago. Updated results from a large clinical
trial now show that one of the newest EGFR-targeted drugs,
osimertinib (Tagrisso), is more effective than earlier EGFR-targeted
therapies in people whose NSCLC tumors have specific alterations in
the EGFR gene.
In patients with advanced NSCLC whose tumors have EGFR
mutations, “osimertinib is now the standard of care for first-line
therapy.”

25. Osimertinib binds to specific mutated forms of EGFR
proteins, including one called T790M that is linked to
resistance to other EGFR-targeted drugs.

26. ● Osimertinib works against tumors with the same EGFR
activating mutations (known as exon 19 deletions and
exon 21 L858R) targeted by the other EGFR-targeted
drugs.
● However, it was also designed to specifically target tumor
cells with an EGFR mutation known as T790M, which has
been shown to cause resistance to the earlier-generation
EGFR-targeted therapies.
● Osimertinib also appears to be more effective than other
EGFR inhibitors in lung cancer that has spread to the
central nervous system (CNS)

27. Osimertinib Tagrisso (osimertinib)
Tagrisso (osimertinib) is a medicine for the treatment of patients with
metastatic non-small cell lung cancer (NSCLC) with a T790M
mutation in the epidermal growth factor receptor (EGFR) gene.

28. 5 Important Areas of Lung Cancer Research
1. Biomarkers
2. Immunotherapy
3. Liquid biopsy
4. Robotics
5. Stereotactic Radiation

29. Biomarkers
Treatments that target specific biomarkers that are present in lung cancer
tumors continue to have great success, especially in treating patients with:
● EGFR
● ALK
● ROS1
● RET
● BRAF
● NTRK
It is recommended that all patients get comprehensive biomarker
testing when they are first diagnosed.

30. A biomarker is a feature of the cancer that can help determine
a personalized treatment. It is advisable for patients to discuss
with their doctors how and when to schedule a complete panel
of biomarker testing. This is preferably before any treatment
is started. Comprehensive biomarker testing, specified in the
NCCN guidelines, will provide the most complete assessment.
This assessment can help to determine the most effective
treatment plan.

32. Immunotherapy
Immunotherapy is another very effective treatment option that uses
the body’s own immune response to fight the cancer without
damaging healthy cells. In the past few years, lung cancer research
has yielded new medications that can be used to stop cancer cells
from being able to turn off the immune system. This allows it to do
its work in battling the cancer.
For some patients who are newly diagnosed with metastatic lung
cancer, the combination of a treatment that helps the immune
system to fight cancer—an immunotherapy—and chemotherapy
may help them to live longer than chemotherapy alone, according to
the results of a large clinical trial.

33. Immune checkpoint inhibitor monoclonal antibodies (Ab)
that block PD-1 proteins target immune cells in the lymph
nodes and immune and cancer cells in tumors.

34. Liquid biopsy
● In addition, various forms of “liquid biopsy” are being studied
that can identify molecular abnormalities of lung cancer
without the need for invasive procedures. These specialized
blood tests make use of readily accessible specimens like blood,
saliva, or even exhaled breath.
● Also known as fluid biopsy or fluid phase biopsy
● Tumors release a variety of biomolecules into the bloodstream
that can be collected via a blood test, separated from the
plasma, and studied. The circulating tumor DNA (ctDNA) and
intact circulating tumor cells (CTCs) are two of the components
that are targeted during a liquid biopsy.

37. Robotics
Lung cancer research has rapidly
advanced robotics used in surgeries,
which allow for quicker recovery for
lung cancer patients who have tumors
resected. Board certified thoracic
surgeons are able to remove the
cancerous tissue with minimally
invasive techniques, which allow for
far smaller incision sites and more
rapid recovery for patients.

38. Stereotactic Radiation
Stereotactic radiation is a type of external radiation
therapy that uses special equipment to position the
patient and precisely deliver radiation to a tumor.
Advances in techniques using stereotactic radiation
allow for effective treatment of brain metastases.

39. The Future for Lung Cancer Treatment Offers Real Hope
● Researchers nationwide are working hard to improve the outlook
for lung cancer—and it’s working. “If you look at cancer stats
the past year, it’s the biggest decrease in cancer deaths that have
been seen in history, and the most reductions in cancer were
seen in lung cancer,”
● Much of that progress is the result of these treatment
innovations, such as new targeted therapies, he says. The future
is bright, but don’t forget: Early detection is key,
● “We could reduce lung cancer deaths even more if more people
got lung cancer screening.”

40. References
[ ] https://www.aacr.org/blog/2019/11/15/lung-cancer-awareness/
[ ] https://www.cancercenter.com/cancer-types/lung-cancer/treatments
[ ] https://www.medicalnewstoday.com/articles/323701#what-is-it
[ ]
https://www.google.co.in/amp/s/www.asbestos.com/blog/2020/10/14/five-areas-lung-canc
er-research/amp/
[ ] https://www.cancer.gov/types/lung/research
[ ] https://lcfamerica.org/lung-cancer-research/
[ ] https://www.spandidos-publications.com/10.3892/ol.2019.10166
[ ] https://www.healthcentral.com/slideshow/lung-cancer-new-treatments