A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed

Abstract

Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized disease or treatment-sensitive cancers and therefore their contributions to cancer curability are relatively limited. The prognosis for cancer patients varies among different cancer types with a five-year relative survival rate (RSR) of more than 80% in thyroid cancer, melanoma, breast cancer, and Hodgkin’s lymphoma. The most dismal prognosis is observed in patients with small-cell lung cancer, pancreatic cancer, hepatocellular carcinoma, oesophagal cancer, acute myeloid leukemia, non-small cell lung cancer, and gastric cancer with a five-year RSR ranging between 7% and 28%. The current review is intended to provide a general view about how much we have achieved in curing cancer as regards to different therapies and cancer types. Finally, we propose a small molecule dual-targeting broad-spectrum anticancer strategy called OncoCiDia, in combination with emerging highly sensitive liquid biopsy, with theoretical curative potential for the management of solid malignancies, especially at the micro-cancer stage.

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

“…However, nearly radical effect was paradoxically discovered in hepatic micro-HCCs [24], which is against earlier consensus that normally tumors smaller than 5 mm lack their own vasculature and are nourished by the blood diffused from their host organs [71]. This counterintuitive observation was reproduced in a rodent model with secondary liver malignancy [72]. Further studies comparing conventional and immunohistochemical (IHC) staining indicated that those micro-cancers looked avascular on H&E stained slide, but CD34 staining revealed an intratumoral network of endothelium, suggesting that such an endothelial network could be 1) functional and vital for supplying nutrients to cancer cells, and 2) vulnerable to VDA attack resulting in nearly complete tumor necrosis [72].…”

“…This counterintuitive observation was reproduced in a rodent model with secondary liver malignancy [72]. Further studies comparing conventional and immunohistochemical (IHC) staining indicated that those micro-cancers looked avascular on H&E stained slide, but CD34 staining revealed an intratumoral network of endothelium, suggesting that such an endothelial network could be 1) functional and vital for supplying nutrients to cancer cells, and 2) vulnerable to VDA attack resulting in nearly complete tumor necrosis [72].…”

“…Micro-cancers of <5 mm in diameter are undetectable by current clinical imaging modalities, but are likely detectable by liquid biopsy. Imagine with a positive screening outcome, the patient may subject to a "blind" OncoCiDia episode, without knowing exactly what and where the original malignancy is, and the few residual cancer cells after CA4P in such micro-cancers can be eradicated under the full coverage of beta radiation emitted by 131 I-Hyp with a 2-3 mm penetration distance [72]. The patient is then re-checked with a follow-up liquid biopsy weeks or months later, if the result turns out to be negative, the patient could become cured.…”

“…By postmortem IHC staining, it was difficult to detect CD34 in necrotic tissue induced by CA4P because, as a transmembrane protein expressed on endothelial cells, CD34 might be destroyed along with drug-induced rupture of cell membrane. Nevertheless, the role of endothelium of tumoral vasculature in cancer ecology and VDA therapeutic response was exposed by setting and comparing treated and control groups [72].…”

“…For future clinical applications, we believe VDA-involved combinatory treatment would provide the super-effective, minimally toxic and depersonalized anticancer therapeutics. In this context, a serial preclinical and clinical trials of OncoCiDia have been ongoing [17,18], including in a particular proof-of principle experiment in animals to verify the curability of micro-cancers by OncoCiDia [72]. In addition, our imaging-based MRI-microangiography-histopathology correlation platform could be broadly applied in assessing in vivo anticancer efficacy of different types of novel agents [89].…”