Li Pin Kao1,2*
1Department of Basic Medical Sciences, Purdue University, Indiana, USA
2 Centre for Cancer Research, Purdue University, Indiana, USA
*Corresponding author:Li Pin Kao, Department of Basic Medical Sciences, Centre for Cancer Research, Purdue University, USA
Submission: February 02, 2018;Published: August 17, 2018
ISSN: 2576-9170 Volume2 Issue3
Breast cancer, the first most common malignant tumor in women worldwide. Many etiological factors such as a wide spectrum of clinical manifestations caused by family clustering, hormonal factors, physiology changed, environmental inducers, and life styles. Although there are many FDA-approval drugs for breast cancers. Tumors are heterogenous and individual has inherited different genetic background. Thus, it is hard to find an effective treatment and it may recurrent after recovery from first treatment.
Keywords:Breast cancer; Autophagy; Autophagy related inhibitors; Chemotherapy
The mortality rate exceeds 144,000 cases and most of the breast cancer (BC) cases are resistant to traditional chemotherapy and radiotherapy. Wide varieties of chemotherapeutic agents have been tried and are in use, including tamoxifen, docetaxel, anthracyclines (i.e. doxorubicin, and epirubicin), taxanes (i.e. paclitaxel, and docetaxel), 5-fluorouracil, cyclophosphamide, and carboplatin. No regimen has been proved to be curative. Often, the response rate and prolongation of survival are minimal (a few months or less), and there is a significant morbidity associated with poor treatment effects. Surgical resection is considered the first-line options for early tumors, although there is no agreement on which the best approach is. Interestingly, triple negative has been reported has higher chemo-resistance than other type of breast cancers with low autophagy activity [1,2]. Antiestrogen resistant cell lines exhibit increased basal autophagy when compared with their antiestrogen sensitive parental cells . Study has shown to manipulate transient receptor potential channel 5 (TRPC5), a Ca2+ permeable cation channel, which helps in promotes autophagic activity . Studies also demonstrate the breast cancer usually Prosurvival after autophagy activity increase by various therapeutics [5-7]. Moreover, Tamoxifen and Faslodex (ICI) both induce autophagy in ER+ breast cancer cells without [3-11]. There are small molecules which has been in FDA-approval drug lists and applied in clinical trial in different diseases.
Antiestrogen resistant cell lines exhibit increased basal autophagy. Study had demonstrated ccombination of Tamoxifen or Faslodex (ICI) with Hydroxychloroquine (HCQ) had different anti-estrogen responsiveness in vitro or in vivo which may affect by tumor microenvironment (i.e. chemokines, macrophage development/activity . Inhibiting autophagy via autophagyrelated genes (i.e. autophagy-related gene (Atg) 5, Atg7, and p62/ SQSTM1) silencing potentiated antiestrogen-mediated cell death, indicating that antiestrogen stimulated autophagy is prosurvival and a critical mechanism of therapy resistance. Overall, it indicated that increased in autophagy activity in early recurring breast cancer when compared with breast cancer that never recurs. Moreover, elevated p62 is significantly correlated with poor survival in breast cancer patients, suggesting a role for autophagy in breast cancer re occurrence. Manipulation of autophagy activity can be a potential therapy for chemotherapy in vitro or in vivo. Therefore, diagnosis or detection at an early stage is crucial to allow the application of treatments for increasing the life expectancy of the patient  (Table 1,2).
Table 1:Autophagy inhibitors during autophagy pathway.
Table 2:Current Hydroxychloroquine (HCQ) clinical trials.
It is very little is known how the manipulation of a biological process toward to potential cancer therapy. As is often the case, we need understand the basic mechanistic of biological processes if this is going to apply for a clinical benefit or other practical application. This article demonstrated the importance of manipulation of autophagy activities in different cancer treatment in basic biomedical research and different clinical trials. Given the rapid progress in understanding autophagy in cancer-related researches and what it does, manipulation of autophagy activities in cancer-related research has ready to take off.
The author would like to acknowledge the financial support of the Purdue University for provided support in the form of salaries of KLP listed but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2018 Li Pin Kao . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and build upon your work non-commercially.