PARTNERSHIP OPPORTUNITIES
24 January, 2024 by Anshul (neobio)
Commonly used treatments for lung cancer, such as systemic chemotherapy and surgery, have a limited scope for providing effective results, as they can often affect both malignant and healthy cells. Usually leading to undesirable side effects, these approaches don’t tend to offer the specificity required for optimal treatment outcomes.
The central driver behind the development of more efficient treatments for Lung Cancer involves directing focus towards the cancer cells themselves, thereby limiting the interference with healthy cells.
Lung cancer is an increasingly prevalent health issue worldwide, with a high incidence and mortality rate. The majority of these cases manifest as a non-small cell lung cancer (NSCLC) histology, signifying the pressing need for more effective treatments that cater to this population.
Lung cancer’s global impact calls for innovative therapeutic solutions that navigate around the limitations of traditional treatments without compromising efficacy.
Traditional lung cancer treatments, which primarily include systemic chemotherapy and surgery, have a limited efficacy with an overall poor survival rate for patients. However, these treatments often cause damaging side effects because they attack both normal and cancer cells.
Moreover, systemic chemotherapy specifically does not possess the level of precision necessary to focus its effects solely on cancer cells. These limitations highlight the need for more targeted forms of treatment.
Over recent years, the increasing knowledge about molecular biology and translational science has led to the identification of diverse driver gene mutations and distinct intracellular pathways in lung cancer. This understanding has, in turn, paved the way for the development of targeted therapies.
These emerging therapies, unlike systemic treatments, can selectively target and disrupt the growth and functioning of cancer cells, leaving normal cells unharmed. The result of this selective targeting is enhanced therapeutic action with minimized side effects.
A key feature of these targeted therapies is their capability to focus their action on specific abnormalities within tumor cells (biomarkers), which can only be identified through specialized tests. Thus, if tests for these biomarkers return positive, the potential for specialized targeted treatments opens up.
In this section, we explore how drug targets are identified, how targeted therapies function, and treatment eligibility.
The key to understanding the science behind drug targets for lung cancer lies in biomarker testing. This testing examines changes in a tumor’s DNA, such as mutations, additions, deletions, or rearrangements, that targeted therapies can address. These DNA changes are what we refer to as biomarkers.
Biomarker testing is integral to identifying which targeted therapy will be the most effective for a specific tumor. Notably, since not every lung cancer patient is eligible for targeted therapies, biomarker testing becomes crucial in determining the best course of action.
Conventional cancer treatment methods can harm healthy cells as they attack cancerous ones, leading to unwanted side effects. In contrast, targeted therapies work by interrupting the growth and functioning of cancer cells directly. In other words, they attack specific targets on or within the tumor cells. The result is often fewer side effects and a more efficient treatment process.
Targeted therapy eligibility is typically determined by specific tests, such as molecular testing or biomarker testing, which identify the presence of certain abnormalities. If a patient does not test positive for a biomarker with an approved targeted therapy, traditional treatments like chemotherapy or immunotherapy, or a combination of the two, may be recommended. Surgery or radiation may also be considered. In some cases, enrolling in a clinical trial looking at treatments for other markers may be appropriate.
Regarding targeted therapies for lung cancer, targets include specific proteins present on cancer cells that contribute to their growth and survival. Therefore, by crafting therapies that can identify and attack these targets, we can effectively halt the progression of the disease.
Some of the common drug targets in lung cancer treatment include EGFR (Epidermal Growth Factor Receptor), ALK (Anaplastic Lymphoma Kinase), VEGF (Vascular Endothelial Growth Factor), PDGF (Platelet-Derived Growth Factor), and PD1 (Programmed Cell Death Protein 1).
EGFR inhibitors, for example, can block the signal from EGFR that tells cells to grow, making them a useful tool in managing NSCLCs with EGFR gene mutations. The ALK gene rearrangement is another common target, producing an abnormal ALK protein that causes cells to grow and spread. Drugs that target the abnormal ALK protein can often shrink tumors in people with this gene change.
First-generation TRK (Tropomyosin Receptor Kinase) inhibitors such as larotrectinib and entrectinib play a significant role in targeted therapy. They have been used instead of chemotherapy in people whose cancers have an ALK gene rearrangement, effectively shrinking tumors for several months or more.
Newer drug targets also show promise in lung cancer treatment. The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) targets certain abnormalities in tumors, offering an effective treatment strategy.
Interestingly, repotrectinib (Augtyro) has demonstrated potential for treating locally advanced or metastatic NSCLC caused by a mutation called a ROS1 fusion. Even in patients who have developed resistance to other ROS1 inhibitors, repotrectinib appears to be effective, signifying its potential as a robust tool in the fight against lung cancer.
Despite the promising advances in targeted therapies and the identification of specific drug targets for lung cancer, we still face certain challenges. One of the most significant issues is the development of acquired drug resistance—a phenomenon where cancer cells that were initially responsive to a particular drug become resistant over time.
When we look at drug targets for lung cancer, it’s clear that while targeted therapies have shown promising results, acquired drug resistance remains a significant hurdle. This resistance typically arises due to mutations in the targeted genes, causing the targeted therapy to become less effective or ineffective. It has been shown that cancer cells can develop new mutations in the EGFR gene after treatment with EGFR inhibitors, leading to resistance to the drug. This is a critical problem that requires ongoing research and the development of new strategies to overcome this resistance and improve the prognosis for patients with lung cancer.
Clinical trials play an integral role in advancing lung cancer treatment. They offer a platform for testing new therapies and combinations of treatments in a controlled environment. This can lead to the discovery of new drug targets for lung cancer, as well as new strategies for overcoming drug resistance.
There is also exciting potential in the use of natural compounds, immune mediators, and multi-target agents in the treatment of lung cancer. For instance, studies have explored the anticancer potential of African medicinal fruits, highlighting their ability to target and kill cancer cells.
Immune mediators, such as those involved in the PD-1/PD-L1 pathway, have also shown promise as predictors of response to certain therapies in NSCLC patients with high tissue-PD-L1 expression.
Lastly, multi-target agents like Berberine have demonstrated both antineoplastic and antimetastatic potential, particularly in the context of lung cancer treatment.
The future of lung cancer treatment is likely to be increasingly personalized and precise, leveraging our growing understanding of the molecular mechanisms of this disease to develop more effective and less toxic therapies.
