ADVANCES IN CANCER MANAGEMENT IN THE LAST DECADE
Cancer is the second leading cause of death globally and an estimated 9.6 million deaths in 2018 were attributed to cancer. 1 in 6 deaths globally is attributed to cancer. There is also a significant economic burden due to cancer. It was estimated that the annual economic cost of cancer in 2010 was US $ 1.16 trillion.
However, it has not been all doom and gloom as far as cancer detection and management is concerned. The past decade especially has seen some outstanding research being carried out in cancer biology and this has resulted in the development of some novel drugs and diagnostic tests for diagnosis and treatment of cancer which has resulted in better care and outcomes for cancer patients.
Keep on reading to get a glimpse of the amazing research work in the field of cancer biology over the last decade.
Development of Checkpoint Inhibitors
Development of immune checkpoint inhibitors is probably one of the most seminal discoveries in the field of cancer biology which blossomed a great deal in the past decade. James P Allison and Tasuku Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine for the development of the immune checkpoint blockade. Their discovery has led to the development of a class of drugs called immune checkpoint inhibitors which have revolutionized cancer management. These drugs form a part of the immunotherapy used in cancer management and ensure the destruction of the cancer cells by the immune system of our body. The two main types of immune checkpoint inhibitor drug classes are described below:
CTL4 Inhibitors– Ipilimumab was the first drug from a novel class of drugs called as CTL4 (cytotoxic T-lymphocyte-associated protein 4) checkpoint inhibitors. It was approved for the treatment of melanoma (skin cancer) by the United States Food and Drug Administration (FDA) in 2011. CTL4 inhibitors kill cancer cells by strengthening the immune system. Cancer cells express the CTL4 protein on their cell surface which prevents their destruction by the immune cells of our body. CTL4 inhibitors block the CTL4 protein expressed by the cancer cells thereby ensuring that they are killed by the immune cells of our body.
PD-1/PD-L1 checkpoint inhibitors- Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab, Cemiplimab, and Avelumab are the drugs from this class which have been approved by the US FDA for the treatment of different cancers. These drugs target a pathway called as the PD-1(Programmed cell death protein 1)/PD-L1 (Programmed death-ligand 1). The PD-1 inhibitor pembrolizumab (Brand name- Keytruda) especially received wide media coverage as it helped cure former US president Jimmy Carter who was suffering from metastatic melanoma (skin cancer) which had spread to his liver and brain. Prior to the advent of immunotherapy, a case like President Carters might have been considered to be untreatable. In 2019, the PD-1 inhibitor Pembrolizumab was approved by the US FDA as a first-line monotherapy for the treatment of Non-Small Cell Lung Cancer (NSCLC. The PD-1/PD-L1 inhibitors class of drugs has revolutionized cancer management and has emerged as a major class of drugs for the treatment of different cancers. Currently, there are a lot of clinical studies underway with these drugs in combination with other anti-cancer drugs and their scope will continue to evolve.
First Gene Therapy for Cancer
In 2017, tisagenlecleucel (KYMRIAH) which is the first gene therapy for cancer treatment was approved by the US FDA. It was approved for the treatment of two types of blood cancer. This drug contains the patient’s own immune cells which are modified in a laboratory so that they can attach to the cancer cells and kill them.
Approval of Palbociclib
Palbociclib was approved for the treatment of breast cancer in 2015. It is the first drug in a novel class of drugs called as CDK4/6 inhibitors and is beneficial in terms of slowing down the cancer progression in breast cancer patients
CancerSEEK
It is a new blood test that can identify eight common cancers ― ovary, liver, esophagus, pancreas, stomach, colorectal, lung, and breast cancer. The cost of a single test is estimated at less than $500. This test will help to detect cancer early which can then result in better outcomes for the patients. This test is currently still in the developmental stage and is not available in the clinic.
Proton Therapy
It is useful for the treatment of cancer. It can be safer and more effective than conventional radiation therapy. New research has shown that proton therapy, when combined with chemotherapy, can cause a reduction in severe side effects. A 2014 report in the journal Radiotherapy and Oncology reported that proton therapy offered additional gain for patients with early stage lymphatic cancer after treatment involving radiotherapy.
Novel Drug Delivery Systems
One of the main issues with cancer chemotherapy has been the side effects. The side effects of the drug are primarily due to large quantities of the drug being delivered to non-specific sites inside our body. In order to improve the safety and efficacy of chemotherapeutic drugs, the development of novel drug delivery systems has gained increasing prominence. One of them is RenovoCath. RenovoCath is a dual balloon infusion catheter for the targeted delivery of chemotherapeutic agents. Currently, it is undergoing a clinical trial in the US for treatment of pancreatic cancer. The data from the trial so far has shown that the delivery of chemotherapeutic agents through RenovoCath extended the lives of pancreatic cancer patients from 14 months to 26 months.
Cancer Vaccines
The past decade saw the approval of the first therapeutic cancer vaccine Provenge for the treatment of advanced prostate cancer. Therapeutic cancer vaccines use the body’s natural ability to fight cancer by mobilizing the immune system to find and eliminate tumor cells. They have the potential to cancer cells without causing many of the side-effects associated with conventional chemotherapeutic drugs. Research is currently underway for developing therapeutic vaccines for other types of cancer like lung cancer, breast cancer and so on.
Note: Please note that this is article is a general overview of the new drug/diagnostic developments in cancer and not the entire in-depth list. For the complete details on individual products and approved indications, please refer to the individual package inserts provided by the manufacturer.
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Dr. Anand Lakhkar is a physician scientist from India. He completed his basic medical education from India and his postgraduate training in pharmacology from the United States. He has a MS degree in pharmacology from New York Medical College, a MS degree in Cancer/Neuro Pharmacology from Georgetown University and a PhD in Pharmacology from New York Medical College where he was the recipient of the Graduate Faculty Council Award for academic and research excellence. His research area of expertise is in pulmonary hypertension, traumatic brain injury and cardiovascular pharmacology. He has multiple publications in international peer-reviewed journals and has presented his research at at prestigious conferences.
References:
- https://www.esmo.org/Oncology-News/CancerSEEK-Promises-Earlier-Detection-of-Cancer
- https://www.onclive.com/conference-coverage/sabcs-2019/palbociclib-realworld-data-indicate-os-benefit-in-hrher2-breast-cancer
- https://www.medscape.com/viewarticle/891491
- https://www.cancerresearch.org/join-the-cause/cancer-immunotherapy-month/30-facts/20
- https://www.nobelprize.org/prizes/medicine/2018/press-release/
- https://www.ema.europa.eu/en/medicines/human/EPAR/kymriah
- https://www.cancerresearch.org/immunotherapy/timeline-of-progress
- https://www.who.int/news-room/fact-sheets/detail/cancer
- Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front Oncol. 2018;8:86. Published 2018 Mar 28. doi:10.3389/fonc.2018.00086
- https://www.wfmz.com/health/health-beat-renovocath-treats-pancreatic-cancer/article_b972f2ea-4bfe-5083-bff7-ed513dfb3e91.html
- https://renovorx.com/products/
- https://www.cancerresearch.org/news/2010/fda-approves-provenge-prostate-cancer-vaccine
- https://www.medicalnewstoday.com/articles/268629.php#what-to-expect
- https://www.cancertodaymag.org/Pages/Summer2019/Focusing-on-Proton-Therapy.aspx
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