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.

Keywords: cancer treatment; curability and cancer epidemiology; survival; theragnostics.

Figure 1

Current major therapeutics for cancer. In the primary site, local treatments, including surgery, imaging-guided interventional procedure, and radiotherapy, can be applied with curative intent. In metastatic disease, surgery, radiotherapy, immunotherapy, targeted therapy, and chemotherapy can be delivered, with palliative or even curative intent. Abbreviations: TACE: transcatheter arterial chemoembolization; APC: antigen-presenting cell; PD-1: programmed death-1; PD-L1: programmed death ligand-1; MHC: major histocompatibility complex; TCR: T cell receptor; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; CD: cluster of differentiation.

Figure 2

The distribution of stage (A) and corresponding five-year relative survival rates (B) by cancer types, based on cases diagnosed in 2010 in nine SEER registries. All data here are accessed from the Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs Research Data, November 2018 Sub (1975–2016). Note: Localized and regional prostate cancer cases are merged as localized/regional cases.

Figure 3

(A) A representative example of rats with liver implantation of rhabdomyosarcoma (R1) 12 h after CA4P treatment. This micro R1 tumour measures 3.3 mm and 2.5 mm in long and short axis diameters, respectively. a: on T2 weighted transverse MRI, an oval hyperintense liver lesion (arrow) appears in the left liver lobe (LL); RL, right liver lobe; S, stomach; and C, colon. b: 15 min after contrast agent Gd-DOTA administration, left liver (LL) lesion is enhanced with a central dark region (arrow) suggestive of necrosis; RL, right liver lobe; S, stomach; and C, colon. c: liver specimen containing the micro R1 tumour (arrow) that is too small to be seen from the surface. d: corresponding microangiography shows the lesion as a filling defect suggestive of necrosis (arrow). e: the lesion (arrow) can be traced on the liver section (upper) and corresponding microangiography (bottom). f: low power HE stained microscopy reveals massive and partial hemorrhagic tumour necrosis with tissue reaction and possible tumour residues at the periphery of this virtually hypo- to avascular R1 tumour. g: higher power HE stained microscopy clearly depicts the central necrosis and peripheral few layers of viable R1 tumour cells without noticeable intratumoural vasculature. h: corresponding immunohistochemical CD34-PAS dual staining microscopy confirms the findings with HE staining. (B) A proposed curative OncoCiDia strategy with mathematical algorithms. In early-stage cancer, after the induction of nearly complete necrosis by systemic administration of a VDA, subsequently administered ¹³¹I labelled hypericin can precipitate in tumour necrosis and the emitted beta particles can fully cover the remaining cancer cells particularly in small solid malignancies or micro-cancers. The upper row simulates macro-cancers, with the lower row simulating micro-cancers.