Current status and future directions of cancer

immunotherapy
For decades, the conventional anticancer treatment strategies have been surgery,
chemotherapy, and radiotherapy . While many of these therapies have offered
substantial benefit for eradication of primary tumors, the incidence of disease relapse is
still a commonly encountered problem that results from residual malignant cells and/or
tumor metastases . Therefore, alternative treatment approaches to eliminate the
resistant tumor cells are warranted .

Cancer immunotherapy is becoming an appealing and attractive strategy among

different therapeutic options over the past years and has showed its power against
malignancies. It utilizes the body's immune system to induce anti-tumor response and
thus cancer can be defeated 9. Most recently, cancer immunotherapy field is growing
tremendously, such as utilization of cancer vaccinations, chimeric antigen receptor
(CAR) T-cell therapy and immune checkpoint blockade therapy Several clinical trials
have investigated their potentials in cancer patients lifesavings , and after witnessing
the amazing effect of cancer immunotherapy it was selected as "2013's Breakthrough of
the Year" by Science magazine .

Our goal in this article is to concisely summarize the molecular bases of immune system
and its relationship with cancer as well as recent developments in cancer immunology.
Cancer immunotherapeutic drugs and their clinical applications will also be discussed in
details. Finally, challenges and future directions of cancer immunotherapy will be
provided based on the previous clinical studies. We hope that this review will be of
interests to both basic cancer immunologists and also clinical oncologists.

Cancer vaccines

Cancer vaccines are the response modifiers working by stimulating or restoring the
ability of immune system to fight cancer . It consists of preventive vaccines and
therapeutic vaccines . The goal of preventive vaccine is preventing cancer from
developing. They are based on antigens carried by infectious agents and easy for the
immune system to recognize as foreign invaders . FDA has approved hepatitis B virus
(HBV) vaccines and human papilloma virus (HPV) vaccines It stimulates the immune
system with tumor antigens, peptides, or whole cancer cells The mechanism involves
activating the immune system with targeted T cells to destroy target cancer cells.
Therapeutic vaccines first directly target the immune system and expand the immune
system's attack on cancer cells. A broadening of the immune response may also be
observed as it might attack additional tumor-specific antigens (antigen spread) In this
therapy, peripheral blood mononuclear cells are isolated from the patient and ex
vivo activated with a recombinant fusion protein consisting of a prostate antigen
prostatic acid phosphatase (PAP) conjugated with granulocyte-macrophage colony-
stimulating factor (GM-CSF), and the cells are then re-infused into the patient to activate
PAP-specific T cells T-VEC can trigger an antitumor immune response in non-injected
lesions. The side effects of cancer vaccines vary from different vaccine formation and
person, and the most commonly reported side effect of cancer vaccines is inflammation
at the site of injection.

Immune checkpoint blockade therapy

Immune checkpoint inhibitors are a class of drugs aimed to increase immune response
against cancer cells . The immune system consists of various checkpoint pathways
focusing on T-cell activation that play an important role in modulating anti-tumor
immunity . Molecules that play a crucial role in checkpoint regulation include the T-cell
surface molecules CTLA-4, PD-1, T-cell immunoglobulin and mucin domain containing
protein 3 (Tim-3), and lymphocyte activation gene-3 (LAG-3) . Tumor expressions of
these markers will results in hyporesponsiveness or even exhaustion of the immune
system 111. As a result, these molecules are highly attractive as targets for removing the
inhibition and enable cytotoxic T cells to attack cancer cell for destruction In 2011, FDA
approved anti-CTLA-4 antibodies ipilimumab for the treatment of metastatic melanoma,
which marked the beginning of a new era for cancer immunotherapy Subsequently,
antibodies against PD-1 pembrolizumab and nivolumab have been approved in 2014,
also for the metastatic melanoma . Nivolumab has also been approved in 2015 for
previously treated advanced or metastatic squamous lung cancer, an approval later
expanded also to small cell lung cancer . In 2016, anti-PD-L1 atezolizumab was
approved for bladder cancer and nivolumab was approved for Hodgkin lymphoma . At
present, more than 100 clinical trials are ongoing to test the efficacy and safety of
immune checkpoint blockers in several cancer types . Checkpoint inhibition is also
associated with a unique spectrum of side effects including gastrointestinal,
dermatologic, endocrine, hepatic, and other less common inflammatory events .
Treatment of moderate or severe side effects requires interruption of the checkpoint
inhibitor and the use of corticosteroid

SUMMARY:

In the past decades, our knowledge about the relationship between cancer and the
immune system has increased considerably. Recent years' success of cancer
immunotherapy including monoclonal antibodies (mAbs), cancer vaccines, adoptive
cancer therapy and the immune checkpoint therapy has revolutionized traditional cancer
treatment. However, challenges still exist in this field. Personalized combination
therapies via new techniques will be the next promising strategies for the future cancer
treatment direction.

SOURCE:

Zhang,H.(2018)Current status and future directions of cancer immunotherapy from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968765/
REACTION:

In summary, with the advent of cancer immunotherapy and recent advances of it, curing
cancer seems to be a real possibility for cancer patients. The development of cancer
vaccines, CAR-T cell and checkpoint inhibitors has revolutionized the cancer treatment.
Combination therapy might be a promising therapeutic strategy to treat cancer in the
future. Recognition and management of toxicities of cancer immunotherapy will also be
a key factor for treatment success. Personalized combination therapies that specifically
drive each patient' cancer biology via new techniques will be the most promising
strategies for cancer treatment.
 Risk Factors and Preventions of Breast Cancer
Breast cancer is one of the most common cancers in women worldwide, accounting for
approximately 570,000 deaths in 2015. Over 1.5 million women (25% of all women with
cancer) are diagnosed with breast cancer every year throughout the world 1,2. In
America, it is estimated that 30% of all new cancer cases (252,710) among women are
breast cancer in 2017 3. Breast cancer is a metastatic cancer and can commonly
transfer to distant organs such as the bone, liver, lung and brain, which mainly accounts
for its incurability. Early diagnosis of the disease can lead to a good prognosis and a
high survival rate. In North American, the 5-year relative survival rate of breast cancer
patients is above 80% due to the timely detection of this disease 4. Mammography is a
widely used screening approach in the detecting of breast cancer and proved to help
reduce the mortality effectively. Other screening methods, such as Magnetic Resonance
Imaging (MRI), which is more sensitive than mammography, have also been
implemented and studied during the last decade 5. There're numerous risk factors such
as sex, aging, estrogen, family history, gene mutations and unhealthy lifestyle, which
can increase the possibility of developing breast cancer 6. Most breast cancer occur in
women and the number of cases is 100 times higher in women than that in men 3.
Although the incidence rate of breast cancer in America increases year after year, the
mortality rate decreases due to the widespread early screenings and advanced medical
therapies. Biological therapies have been developed in recent years and proved to be
beneficial for breast cancer. Here, we will focus on studies of the pathogenesis, related
genes, risk factors and preventions of breast cancer over the past years.

SUMMARY

Breast cancer is the second leading cause of cancer deaths among women. The
development of breast cancer is a multi-step process involving multiple cell types, and
its prevention remains challenging in the world. Early diagnosis of breast cancer is one
of the best approaches to prevent this disease. In some developed countries, the 5-year
relative survival rate of breast cancer patients is above 80% due to early prevention. In
the recent decade, great progress has been made in the understanding of breast cancer
as well as in the development of preventative methods. The pathogenesis and tumor
drug-resistant mechanisms are revealed by discovering breast cancer stem cells, and
many genes are found related to breast cancer. Currently, people have more drug
options for the chemoprevention of breast cancer, while biological prevention has been
recently developed to improve patients' quality of life. In this review, we will summarize
key studies of pathogenesis, related genes, risk factors and preventative methods on
breast cancer over the past years. These findings represent a small step in the long
fight against breast cancer.

SOURCE

Sun,Y.(2017)Risk Factors and Preventions of Breast Cancer from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715522/

REACTION

Breast cancer is the most frequently diagnosed cancer in women across 140 countries .
Approximately 1 in 8 women worldwide have a lifetime risk of developing breast
cancer Breast cancer develops through a multistep process, and the pathogenesis of
this disease has not yet been elucidated. Breast cancer is also influenced by genetic
and environmental factors. Targeted prevention strategies against these risk factors
should be taken ahead of time. breast cancer is preventable. Reducing risk factors and
taking chemoprevention are two main measures to prevent breast cancer. However,
there's a long way to go in creating public breast cancer awareness The fear of adverse
effects and lack of understanding of breast cancer might be attributable for this
unwillingness. Although, the Gail model or the IBIS model is widely used for determining
the risk of breast cancer based on a woman's age, family history, race and reproductive
factors, we still lack a reliable strategy to exactly evaluate the risk ratio of breast cancer.
With improvements in sequencing technology, individual genome sequencing may be a
powerful method to evaluate the risk of breast cancer. Better medicines with less
adverse effects and a favorable risk-benefit ratio need to be developed in the future.
 JOURNAL READING

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RLE 106

Submitted to:

Socorro D. Aquino, RN, MaEd, MAN

Submitted by:

Desirie Esteves