Theranostic Approaches for Combating Cancers
Preeti Solanki1, *, Chayanika Putatunda2, Rashmi Sharma3 1 Multidisciplinary Research Unit, Pt. B. D. Sharma, PGIMS, Rohtak, Haryana 124001, India
2 Dept. of Microbiology, Om Sterling Global University, NH-52, Hisar-Chandigarh Road, Hisar, Haryana 125001, India
3 Dept. of Microbiology, DAV University, Jalandhar, Punjab, India
Abstract
Cancer theranostics has witnessed the new era translational medicine leading to the development of new treatment possibilities for cancer patients. The approach of ‘one-size-fits-all’ has changed from traditional methods of surgery, chemo- and radiotherapy to that of personalised cancer medicine, molecular targeted therapy, cancer immunotherapy, nanomedicine, alternative medicine and integrative therapy. The clinical trials for cancer drugs have complicated, requiring better regulatory and health policies, and collaborative efforts from the stakeholders involved in cancer drug discovery and development. A lot has been achieved, mainly in terms of knowledge and biological data, and the same is needed to be integrated and implemented into the development of successful cancer theranostics. The tumour heterogeneity still poses a challenge for scientists, but the last decade has paved a concrete pathway for the future in precise and personalised cancer therapy.
Keywords: Alternative Medicine, Cancer Theranostics, Clinical Trials, Immunotherapy, Integrative Therapy, Molecular Targeted Therapy, Nanomedicine, Personalised Medicine.
* Corresponding author Preeti Solanki: Department of Microbiology, DAV University, Jalandhar, Punjab, India; Tel:(+91)- 99580 67130; E-mail: [email protected] INTRODUCTION
The increasing availability of diagnostic strategies and new health policies have made the possibility of early diagnosis of cancer in the middle- and higher-income groups. However, it is still not feasible for the lower-income groups, especially in the developing and under-developed nations. The choice of traditional treatment options used individually or in combination to combat the complex and resistant nature of cancer, depend on both the patient and the type of cancer (Table 1). The factors affecting the effectiveness of any treatment include the patient’s age overall health, stage of cancer, location/ tissue/ organ affected, besides many other factors still being elucidated by scientists and physicians worldwide. By far,
chemotherapy has been the limited choice of treatment, even with its low efficiency, side effects and economic burden.
Table 1 Generic treatments available for cancer treatment [1-4]. Standard Cancer Treatments | Target | Method | Limitation |
Surgery | Solid tumors, non-metastatic | Excising easily accessible tumours | Does not treat metastatic tumors |
Radiation Therapy | Metastatic cancers | High doses of radiation and drugs | Damage healthy cells, limited specificity |
Chemo-Therapy |
Immuno-Therapy | Metastatic cancers | Harness the patient’s immune response to cancer cells | Limited availability of targetable antigens or ‘neoantigens’ |
The last decade has seen technological advancement in biological research in terms of both techniques and biological databases. Cancer, being the world’s second leading cause of death, has hence, been the most sought after for its treatment possibilities, keeping in mind the limitations of the standard treatment available. The new era of personalised medicine, nanotechnology and computer-aided drug designing have further paved the way for patient-wise treatment optimisation, which in long terms will even prove to be economical, besides having increased efficiency and lesser or no side effects [1-4].
LIMITATIONS OF CONVENTIONAL THERAPY
The mainstay of conventional treatment methods of cancer includes radiation therapy, chemotherapy and surgery. Depending on the situation, these approaches may be used alone or in combinations. Radiotherapy or radiation therapy employs ionizing radiations like X-rays and gamma-rays for the treatment of cancer. It has also been used for palliative care of patients. The radiations act as physical mutagens and tend to damage the DNA of the cells directly or indirectly via generation of free radicals [5]. The damages and breaks in the genetic material of cells lead to cell death via a variety of pathways like apoptosis, mitotic cell death, necrosis, autophagy and senescence [6, 7].
Although the target of radiotherapy is to kill the cancerous cells, the normal cells also tend to get damaged due to the radiations. Such normal cell damage may lead to a variety of symptoms which may appear weeks, months or even years after the radiotherapy. Many symptoms/syndromes/diseases have been observed in the patients subjected to radiotherapy like radiation-induced liver disease [8], radiation pneumonitis [9], rectal injury [10], radiation dermatitis. Radiation-induced liver disease also referred to as radiation hepatitis, has been reported to appear in patients within two weeks to 4 months of receiving hepatic radiotherapy [11]. The clinical symptoms of radiation pneumonitis generally appear within eight months of radiotherapy with the classic symptoms of dyspnea on exertion, non-productive cough, and hypoxemia [12]. Radiation dermatitis may range from the milder form characterized by faint erythema and mild desquamation to severe form characterized by skin necrosis or ulceration [13]. Lawrence et al. [14] have reported esophageal dysmotility, and benign stricture may result from esophageal irradiation while gastric ulceration may result from gastric irradiation.
Earlier it was thought that only the cells directly coming in contact with radiations were affected. However, now more and more awareness about the phenomenon of ‘bystander effect’ is emerging. In the bystander effect, directly irradiated cells transmit specific damaging signals to non-irradiated cells as a result of which the non-irradiated cells also display a response similar to that of irradiated cells [15] which in turn may lead to tissue atrophy as well as the development of secondary tumors [16, 17].
Another conventional cancer treatment approach involves chemotherapy. The major categories of anticancer drugs include alkylating agents, anti-metabolites, microtubule target-agents, epipodophyllotoxins, antibiotics, among others [18]. Although conventional chemotherapy is a mainstay of cancer treatment, it is associated with a wide variety of side effects and complications. These side-effects not only affect the quality of the patient’s life, but in many cases, may be life-threatening. Alkylating agents have been associated with local tissue necrosis, pulmonary fibrosis, hemorrhagic cystitis, nausea, vomiting, diarrhea, alopecia, sterility, among others [19, 20]. Elevated doses of some alkylating drugs have also been associated with reversible heart failure and in life-threatening arrhythmias [21]. Another classical category of chemotherapeutic ag...